人脐带间充质干细胞增强全反式维甲酸对HL-60细胞的诱导分化作用
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摘要
间充质干细胞(MSC)是一种具有自我更新能力和多向分化潜能的成体干细胞,它存在于多种组织中,如胎儿肝脏、胎血、胎儿骨髓、胎肺、脐血、胎盘、脐带、成人骨髓和脂肪等,已经成为组织工程和再生医学细胞治疗的主要候选干细胞之一。其中研究比较广泛的是骨髓间充质干细胞(BMMSC),但骨髓间充质干细胞需要进行骨穿才能得到,对供者有一定的损伤还有感染的可能。人脐带间充质干细胞(hUCMSC)与其他来源的间充质干细胞相比,更容易获得和在体外扩增,并且被病毒感染的概率明显降低,因此hUCMSC是众多来源间充质干细胞中更具有应用价值的种子细胞。
急性早幼粒白血病(APL)不同与其他急性髓系白血病,具有独特的病理特征。在全反式维甲酸(ATRA)应用于治疗APL以前,病人极容易因大量出血而死亡。由于APL细胞具有因染色体易位产生的PML/RARA融合基因,因此早幼粒细胞不能向成熟的单核细胞或粒细胞分化。为了深入研究APL和其他的白血病,研究者从病人体内分离或对正常细胞进行分子生物学操作得到了多种白血病细胞系,如：HL-60、NB-4、KG-1a和K562等。HL-60细胞是从M-2型病人体内分离得到的早幼粒细胞,在不同的刺激下可向成熟的粒系细胞或单核／巨噬细胞分化,是个很好的研究急性白血病和粒系细胞分化的细胞模型。
本研究探讨了人脐带间充质干细胞(hUCMSC)对全反式维甲酸(ATRA)诱导HL-60细胞分化以及对HL-60增殖的影响。HL-60细胞分为4组：未经ATRA处理的对照组、与hUCMSC细胞共培养的hUCMSC组,经ATRA处理的ATRA组以及经ATRA处理并与hUCMSC细胞共培养的ATRA+hUCMSC组。在规定时间采用Cell Counting Kit-8 (CCK8)检测对照组和hUCMSC组HL-60细胞的增殖情况；在光镜下观察各组细胞形态、硝基四氮唑蓝(NBT)阳性细胞；应用real-timePCR方法检测c-myc基因表达水平以及流式细胞术检测CDllb表面标志来比较各组中HL-60细胞的分化情况。结果表明：共培养体系中hUCMSC细胞能抑制HL-60的增殖(hUCMSC:HL-60为1：1时,48h P<0.05,72h P<0.01; hUCMSC:HL-60为1：5时,72h P＜0.05)。在2μmol/L ATRA的刺激下,ATRA+hUCMSC组与ATRA组相比,ATRA+hUCMSC组出现更多具有中性粒细胞形态的HL-60细胞并具更高的NBT阳性率(P<0.05); ATRA+hUCMSC组中HL-60细胞c-myc基因表达水平更低(P<0.05); ATRA+hUCMSC组中HL-60细胞表面CD11b的表达水平更高(48hP＜0.05,72h P＜0.01)。
此外我们还研究了hUCMSC对1,25(OH)2D3诱导HL-60细胞分化的影响。在1,25(OH)2D3的刺激下,用流式细胞技术检测HL-60细胞表面CD11b和CD14的表达水平。与hUCMSC共培养后,HL-60的CD11b表达水平明显上升了,但其CD14的表达水平没有明显变化。
结论：脐带间充质干细胞能抑制HL-60的增殖,增强ATRA对HL-60细胞的诱导分化作用并且hUCMSC细胞自身也能诱导HL-60细胞分化成熟。
This study was aimed to investigate the enhancement of all-trans retinoic acid-induced HL-60 leukemia cell differentiation by umbilical cord mesenchymal stem cell. The HL-60 cells were divided into four groups:control group without ATRA treatment, hUCMSC group co-cultured with hUCMSCs, ATRA group with ATRA treatment as well as ATRA+hUCMSC group with ATRA treatment and co-cultivation with hUCMSCs. The proliferation of control group and hUCMSC group was compared by Cell Counting Kit-8 (CCK8). The morphology of HL-60 cells and NBT positive rate in four groups were observed and compared by microscopy, the c-myc expression of HL-60 cells in different groups was evaluated by real-time PCR, and the CDllb expression on HL-60 cells in different groups were detected by flow cytometry. The results showed that, in the co-culturing system, hUCMSCs can inhibit the proliferation of HL-60 (hUCMSC:HL-60 is 1:1,48h P<0.05,72h P<0.01; hUCMSC:HL-60 is 1:5, 72h P<0.05). With ATRA treatment, compared ATRA+hUCMSC group with ATRA group, there are more neutrophil like HL-60 cells and higher NBT positive rate (P<0.05) in ATRA+hUCMSC group. The c-myc expression of HL-60 cells in ATRA+hUCMSC group was lower than ATRA group (P<0.05). Furthermore, HL-60 cells in ATRA+hUCMSC group had stronger CD11b expression than ATRA group (48h P<0.05, 72h P<0.01). It is concluded that hUCMSC not only can inhibition the proliferation of HL-60 cells, but also can enhance the differentiation potential of ATRA on HL-60 cells.
In addition, we also investigate the effects of hUCMSCs on the HL-60 differetiation induced by 1,25(OH)2D3. When treated by 1,25(OH)2D3, we use flow cytometry to test the expression of CD11b and CD 14 on the HL-60 cells. After co-culturing on the hUCMSC, there is an enhancement of CDllb on the HL-60 cells, but there is no significant change of the expression of CD 14. In some degree, hUCMSCs also can enhance the differentiation effects of 1,25(OH)2D3, while 1,25(OH)2D3 can induce HL-60 cells to neutrophil like cells rather than macrophage cells on hUCMSCs.
急性早幼粒白血病(APL)不同与其他急性髓系白血病,具有独特的病理特征。在全反式维甲酸(ATRA)应用于治疗APL以前,病人极容易因大量出血而死亡。由于APL细胞具有因染色体易位产生的PML/RARA融合基因,因此早幼粒细胞不能向成熟的单核细胞或粒细胞分化。为了深入研究APL和其他的白血病,研究者从病人体内分离或对正常细胞进行分子生物学操作得到了多种白血病细胞系,如：HL-60、NB-4、KG-1a和K562等。HL-60细胞是从M-2型病人体内分离得到的早幼粒细胞,在不同的刺激下可向成熟的粒系细胞或单核／巨噬细胞分化,是个很好的研究急性白血病和粒系细胞分化的细胞模型。
本研究探讨了人脐带间充质干细胞(hUCMSC)对全反式维甲酸(ATRA)诱导HL-60细胞分化以及对HL-60增殖的影响。HL-60细胞分为4组：未经ATRA处理的对照组、与hUCMSC细胞共培养的hUCMSC组,经ATRA处理的ATRA组以及经ATRA处理并与hUCMSC细胞共培养的ATRA+hUCMSC组。在规定时间采用Cell Counting Kit-8 (CCK8)检测对照组和hUCMSC组HL-60细胞的增殖情况；在光镜下观察各组细胞形态、硝基四氮唑蓝(NBT)阳性细胞；应用real-timePCR方法检测c-myc基因表达水平以及流式细胞术检测CDllb表面标志来比较各组中HL-60细胞的分化情况。结果表明：共培养体系中hUCMSC细胞能抑制HL-60的增殖(hUCMSC:HL-60为1：1时,48h P<0.05,72h P<0.01; hUCMSC:HL-60为1：5时,72h P＜0.05)。在2μmol/L ATRA的刺激下,ATRA+hUCMSC组与ATRA组相比,ATRA+hUCMSC组出现更多具有中性粒细胞形态的HL-60细胞并具更高的NBT阳性率(P<0.05); ATRA+hUCMSC组中HL-60细胞c-myc基因表达水平更低(P<0.05); ATRA+hUCMSC组中HL-60细胞表面CD11b的表达水平更高(48hP＜0.05,72h P＜0.01)。
此外我们还研究了hUCMSC对1,25(OH)2D3诱导HL-60细胞分化的影响。在1,25(OH)2D3的刺激下,用流式细胞技术检测HL-60细胞表面CD11b和CD14的表达水平。与hUCMSC共培养后,HL-60的CD11b表达水平明显上升了,但其CD14的表达水平没有明显变化。
结论：脐带间充质干细胞能抑制HL-60的增殖,增强ATRA对HL-60细胞的诱导分化作用并且hUCMSC细胞自身也能诱导HL-60细胞分化成熟。
This study was aimed to investigate the enhancement of all-trans retinoic acid-induced HL-60 leukemia cell differentiation by umbilical cord mesenchymal stem cell. The HL-60 cells were divided into four groups:control group without ATRA treatment, hUCMSC group co-cultured with hUCMSCs, ATRA group with ATRA treatment as well as ATRA+hUCMSC group with ATRA treatment and co-cultivation with hUCMSCs. The proliferation of control group and hUCMSC group was compared by Cell Counting Kit-8 (CCK8). The morphology of HL-60 cells and NBT positive rate in four groups were observed and compared by microscopy, the c-myc expression of HL-60 cells in different groups was evaluated by real-time PCR, and the CDllb expression on HL-60 cells in different groups were detected by flow cytometry. The results showed that, in the co-culturing system, hUCMSCs can inhibit the proliferation of HL-60 (hUCMSC:HL-60 is 1:1,48h P<0.05,72h P<0.01; hUCMSC:HL-60 is 1:5, 72h P<0.05). With ATRA treatment, compared ATRA+hUCMSC group with ATRA group, there are more neutrophil like HL-60 cells and higher NBT positive rate (P<0.05) in ATRA+hUCMSC group. The c-myc expression of HL-60 cells in ATRA+hUCMSC group was lower than ATRA group (P<0.05). Furthermore, HL-60 cells in ATRA+hUCMSC group had stronger CD11b expression than ATRA group (48h P<0.05, 72h P<0.01). It is concluded that hUCMSC not only can inhibition the proliferation of HL-60 cells, but also can enhance the differentiation potential of ATRA on HL-60 cells.
In addition, we also investigate the effects of hUCMSCs on the HL-60 differetiation induced by 1,25(OH)2D3. When treated by 1,25(OH)2D3, we use flow cytometry to test the expression of CD11b and CD 14 on the HL-60 cells. After co-culturing on the hUCMSC, there is an enhancement of CDllb on the HL-60 cells, but there is no significant change of the expression of CD 14. In some degree, hUCMSCs also can enhance the differentiation effects of 1,25(OH)2D3, while 1,25(OH)2D3 can induce HL-60 cells to neutrophil like cells rather than macrophage cells on hUCMSCs.
引文
1. Karahuseyinoglu S, Cinar O, Kilic E, Kara F, Akay GG, Demiralp DO, Tukun A, Uckan D, Can A:Biology of stem cells in human umbilical cord stroma:in situ and in vitro surveys. Stem Cells 2007,25(2):319-331.
2. Tsai PC, Fu TW, Chen YM, Ko TL, Chen TH, Shih YH, Hung SC, Fu YS:The therapeutic potential of human umbilical mesenchymal stem cells from Wharton's jelly in the treatment of rat liver fibrosis. Liver Transpl 2009, 15(5):484-495.
3. Liao W, Xie J, Zhong J, Liu Y, Du L, Zhou B, Xu J, Liu P, Yang S, Wang J et al: Therapeutic effect of human umbilical cord multipotent mesenchymal stromal cells in a rat model of stroke. Transplantation 2009,87(3):350-359.
4. Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S, Luo Y, Rao MS, Velagaleti G, Troyer D:Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease. Stem Cells 2006,24(3):781-792.
5. Friedman R, Betancur M, Boissel L, Tuncer H, Cetrulo C, Klingemann H: Umbilical cord mesenchymal stem cells:adjuvants for human cell transplantation. Biol Blood Marrow Transplant 2007,13(12):1477-1486.
6. Conget PA, Minguell JJ:Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 1999, 181(1):67-73.
7. Haynesworth SE, Baber MA, Caplan AI:Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro:effects of dexamethasone and IL-1 alpha. J Cell Physiol 1996,166(3):585-592.
8. Liu M, Yang SG, Shi L, Du WT, Liu PX, Xu J, Gu DS, Liang L, Dong CL, Han ZC:Mesenchymal stem cells from bone marrow show a stronger stimulating effect on megakaryocyte progenitor expansion than those from non-hematopoietic tissues. Platelets 2010,21(3):199-210.
9. Zhu Y, Sun Z, Han Q, Liao L, Wang J, Bian C, Li J, Yan X, Liu Y, Shao C et al: Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukemia 2009,23(5):925-933.
10. Filmus J, Buick RN:Relationship of c-myc expression to differentiation and proliferation of HL-60 cells. Cancer Res 1985,45(2):822-825.
11. Wallington LA, Durham J, Bunce CM, Brown G:Growth of single HL60 cells in liquid culture:analysis of the influences of differentiative agents. Leuk Res 1996,20(10):821-829.
12. Golomb HM, Rowley JD, Vardiman JW, Testa JR, Butler A:"Microgranular" acute promyelocytic leukemia:a distinct clinical, ultRAStructural, and cytogenetic entity. Blood 1980,55(2):253-259.
13. Tomonaga M, Yoshida Y, Tagawa M, Jinnai I, Kuriyama K, Amenomori T, Yoshioka A, Matsuo T, Nonaka H, Ichimaru M:Cytochemistry of acute promyelocytic leukemia (M3):leukemic promyelocytes exhibit heterogeneous patterns in cellular differentiation. Blood 1985, 66(2):350-357.
14. Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY:Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988,72(2):567-572.
15. Breitman TR, Selonick SE, Collins SJ:Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci USA 1980,77(5):2936-2940.
16. Nervi C, Ferrara FF, Fanelli M, Rippo MR, Tomassini B, Ferrucci PF, Ruthardt M, Gelmetti V, Gambacorti-Passerini C, Diverio D et al: Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion protein. Blood 1998,92(7):2244-2251.
17. Briquet A, Dubois S, Bekaert S, Dolhet M, Beguin Y, Gothot A:Prolonged ex vivo culture of human bone marrow mesenchymal stem cells influences their supportive activity toward NOD/SCID-repopulating cells and committed progenitor cells of B lymphoid and myeloid lineages. Haematologica,95(1):47-56.
1. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C:Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7). A report of the French-American-British Cooperative Group. Ann Intern Med 1985,103(3):460-462.
2. Minucci S, Pelicci PG:Determinants of oncogenic transformation in acute promyelocytic leukemia:the hetero-union makes the force. Cancer Cell 2007, 12(1):1-3.
3. Zhu J, Nasr R, Peres L, Riaucoux-Lormiere F, Honore N, Berthier C, Kamashev D, Zhou J, Vitoux D, Lavau C et al: RXR is an essential component of the oncogenic PML/RARA complex in vivo. Cancer Cell 2007,12(1):23-35.
4. Salomoni P, Pandolfi PP:The role of PML in tumor suppression. Cell 2002, 108(2):165-170.
5. Stone RM, Mayer RJ:The unique aspects of acute promyelocytic leukemia. J Clin Oncol 1990,8(11):1913-1921.
6. Kelly K, Cochran BH, Stiles CD, Leder P:Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell 1983,35(3 Pt 2):603-610.
7. Dalla-Favera R, Wong-Staal F, Gallo RC:Onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary leukaemic cells of the same patient. Nature 1982,299(5878):61-63.
8. Grosso LE, Pitot HC:Transcriptional regulation of c-myc during chemically induced differentiation of HL-60 cultures. Cancer Res 1985,45(2):847-850.
9. Wolf D, Rotter V:Major deletions in the gene encoding the p53 tumor antigen cause lack of p53 expression in HL-60 cells. Proc Natl Acad Sci USA 1985,82(3):790-794.
10. Naharro G, Robbins KC, Reddy EP:Gene product of v-fgr one:hybrid
protein containing a portion of actin and a tyrosine-specific protein kinase. Science 1984,223(4631):63-66.
11. Gee CE, Griffin J, Sastre L, Miller LJ, Springer TA, Piwnica-Worms H, Roberts TM:Differentiation of myeloid cells is accompanied by increased levels of pp60c-src protein and kinase activity. Proc Natl Acad Sci U S A 1986, 83(14):5131-5135.
12. Sariban E, Mitchell T, Kufe D:Expression of the c-fms proto-oncogene during human monocytic differentiation. Nature 1985,316(6023):64-66.
13. Lanotte M, Martin-Thouvenin V, Najman S, Balerini P, Valensi F, Berger R: NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3). Blood 1991,77(5):1080-1086.
14. Hu ZB, Ma W, Uphoff CC, Lanotte M, Drexler HG:Modulation of gene expression in the acute promyelocytic leukemia cell line NB4. Leukemia 1993, 7(11):1817-1823.
15. Duprez E, Ruchaud S, Houge G, Martin-Thouvenin V, Valensi F, Kastner P, Berger R, Lanotte M:A retinoid acid 'resistant't(15;17) acute promyelocytic leukemia cell line:isolation, morphological, immunological, and molecular features. Leukemia 1992,6(12):1281-1287.
16. Dermime S, Grignani F, Clerici M, Nervi C, Sozzi G, Talamo GP, Marchesi E, Formelli F, Parmiani G, Pelicci PG et al: Occurrence of resistance to retinoic acid in the acute promyelocytic leukemia cell line NB4 is associated with altered expression of the pml/RAR alpha protein. Blood 1993, 82(5):1573-1577.
17. Fibach E, Hayashi M, Sachs L:Control of normal differentiation of myeloid leukemic cells to macrophages and granulocytes. Proc Natl Acad Sci U S A 1973,70(2):343-346.
18. Paran M, Sachs L, Barak Y, Resnitzky P:In vitro induction of granulocyte differentiation in hematopoietic cells from leukemic and non-leukemic
patients. Proc Natl Acad Sci USA 1970,67(3):1542-1549.
19. Breitman TR, Selonick SE, Collins SJ:Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci USA 1980,77(5):2936-2940.
20. Breitman TR, Collins SJ, Keene BR:Terminal differentiation of human promyelocytic leukemic cells in primary culture in response to retinoic acid. Blood 1981,57(6):1000-1004.
21. Runde V, Aul C, Sudhoff T, Heyll A, Schneider W:Retinoic acid in the treatment of acute promyelocytic leukemia:inefficacy of the 13-cis isomer and induction of complete remission by the all-trans isomer complicated by thromboembolic events. Ann Hematol 1992,64(6):270-272.
22. Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY:Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988,72(2):567-572.
23. Wang ZY:Ham-Wasserman lecture:treatment of acute leukemia by inducing differentiation and apoptosis. Hematology Am Soc Hematol Educ Program 2003:1-13.
24. Collins SJ:Retinoic acid receptors, hematopoiesis and leukemogenesis. Curr Opin Hematol 2008,15(4):346-351.
25. Wang ZY, Chen Z:Acute promyelocytic leukemia:from highly fatal to highly curable. Blood 2008,111(5):2505-2515.
26. Scaglioni PP, Pandolfi PP:The theory of APL revisited. Curr Top Microbiol Immunol.2007,313:85-100.
27. Zheng PZ, Wang KK, Zhang QY, Huang QH, Du YZ, Zhang QH, Xiao DK, Shen SH, Imbeaud S, Eveno E et al: Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A 2005,102(21):7653-7658.
28. Park DJ, Vuong PT, de Vos S, Douer D, Koeffler HP:Comparative analysis of genes regulated by PML/RAR alpha and PLZF/RAR alpha in response to retinoic acid using oligonucleotide arrays. Blood 2003,102(10):3727-3736.
29. Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, Zhu J, Tang W, Sun GL, Yang KQ et al: Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL):Ⅱ. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 1997,89(9):3354-3360.
30. Lu DP, Qiu JY, Jiang B, Wang Q, Liu KY, Liu YR, Chen SS:Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia:a pilot report. Blood 2002,99(9):3136-3143.
31. Chen GQ, Shi XG, Tang W, Xiong SM, Zhu J, Cai X, Han ZG, Ni JH, Shi GY, Jia PM et al: Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL):Ⅰ. As2O3 exerts dose-dependent dual effects on APL cells. Blood 1997,89(9):3345-3353.
32. Matsui W, Smith BD, Vala M, Beal N, Huff CA, Diehl LF, Jones RJ: Requirement for myeloid growth factors in the differentiation of acute promyelocytic leukaemia. Br JHaematol 2005,128(6):853-862.
33. Kakizuka A, Miller WH, Jr., Umesono K, Warrell RP, Jr., Frankel SR, Murty VV, Dmitrovsky E, Evans RM:Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell 1991,66(4):663-674.
34. Melnick A, Licht JD:Deconstructing a disease:RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood 1999,93(10):3167-3215.
35. Shih LY, Kuo MC, Liang DC, Huang CF, Lin TL, Wu JH, Wang PN, Dunn P, Lai CL:Internal tandem duplication and Asp835 mutations of the FMS-like tyrosine kinase 3 (FLT3) gene in acute promyelocytic leukemia. Cancer 2003, 98(6):1206-1216.
36. Nervi C, Ferrara FF, Fanelli M, Rippo MR, Tomassini B, Ferrucci PF, Ruthardt M, Gelmetti V, Gambacorti-Passerini C, Diverio D et al: Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion protein. Blood 1998,92(7):2244-2251.
37. Zhu J, Gianni M, Kopf E, Honore N, Chelbi-Alix M, Koken M, Quignon F, Rochette-Egly C, de The H:Retinoic acid induces proteasome-dependent degradation of retinoic acid receptor alpha (RARalpha) and oncogenic RARalpha fusion proteins. Proc Natl Acad Sci U S A 1999, 96(26):14807-14812.
38. Lallemand-Breitenbach V, Zhu J, Puvion F, Koken M, Honore N, Doubeikovsky A, Duprez E, Pandolfi PP, Puvion E, Freemont P et al: Role of promyelocytic leukemia (PML) sumolation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor alpha degradation. J Exp Med 2001,193(12):1361-1371.
39. Muller S, Matunis MJ, Dejean A:Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleus. Embo J 1998,17(1):61-70.
40. Kamashev D, Vitoux D, De The H:PML-RARA-RXR oligomers mediate retinoid and rexinoid/cAMP cross-talk in acute promyelocytic leukemia cell differentiation. JExp Med 2004,199(8):1163-1174.
41. Liu TX, Zhang JW, Tao J, Zhang RB, Zhang QH, Zhao CJ, Tong JH, Lanotte M, Waxman S, Chen SJ et al: Gene expression networks underlying retinoic acid-induced differentiation of acute promyelocytic leukemia cells. Blood 2000,96(4):1496-1504.
42. Rocca B, Morosetti R, Habib A, Maggiano N, Zassadowski F, Ciabattoni G, Chomienne C, Papp B, Ranelletti FO:Cyclooxygenase-1, but not -2, is upregulated in NB4 leukemic cells and human primary promyelocytic blasts during differentiation. Leukemia 2004,18(8):1373-1379.
43. Kini AR, Peterson LA, Tallman MS, Lingen MW:Angiogenesis in acute promyelocytic leukemia:induction by vascular endothelial growth factor and inhibition by all-trans retinoic acid. Blood 2001,97(12):3919-3924.
44. Zhu J, Guo WM, Yao YY, Zhao WL, Pan L, Cai X, Ju B, Sun GL, Wang HL, Chen SJ et al: Tissue factors on acute promyelocytic leukemia and endothelial cells are differently regulated by retinoic acid, arsenic trioxide and chemotherapeutic agents. Leukemia 1999,13(7):1062-1070.
45. Pendino F, Flexor M, Delhommeau F, Buet D, Lanotte M, Segal-Bendirdjian E: Retinoids down-regulate telomeRASe and telomere length in a pathway distinct from leukemia cell differentiation. Proc Natl Acad Sci U S A 2001, 98(12):6662-6667.
46. Tarkanyi I, Dudognon C, Hillion J, Pendino F, Lanotte M, Aradi J, Segal-Bendirdjian E:Retinoid/arsenic combination therapy of promyelocytic leukemia:induction of telomeRASe-dependent cell death. Leukemia 2005, 19(10):1806-1811.
47. Tarrade A, Bastien J, Bruck N, Bauer A, Gianni M, Rochette-Egly C:Retinoic acid and arsenic trioxide cooperate for apoptosis through phosphorylated RXR alpha. Oncogene 2005,24(14):2277-2288.
48. Zhu J, Lallemand-Breitenbach V, de The H:Pathways of retinoic acid- or arsenic trioxide-induced PML/RARalpha catabolism, role of oncogene degradation in disease remission. Oncogene 2001,20(49):7257-7265.
49. Zhao Q, Tao J, Zhu Q, Jia PM, Dou AX, Li X, Cheng F, Waxman S, Chen GQ, Chen SJ et al:Rapid induction of cAMP/PKA pathway during retinoic acid-induced acute promyelocytic leukemia cell differentiation. Leukemia 2004,18(2):285-292.
50. Leung J, Pang A, Yuen WH, Kwong YL, Tse EW:Relationship of expression of aquaglyceroporin 9 with arsenic uptake and sensitivity in leukemia cells. Blood 2007,109(2):740-746.
51. Liu M, Lee MH, Cohen M, Bommakanti M, Freedman LP:Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev 1996, 10(2):142-153.
52. Verlinden L, Verstuyf A, Convents R, Marcelis S, Van Camp M, Bouillon R: Action of 1,25(OH)2D3 on the cell cycle genes, cyclin D1, p21 and p27 in MCF-7 cells. Mol Cell Endocrinol 1998,142(1-2):57-65.
53. Jensen SS, Madsen MW, Lukas J, Binderup L, Bartek J:Inhibitory effects of lalpha,25-dihydroxyvitamin D(3) on the G(1)-S phase-controlling machinery. Mol Endocrinol 2001,15(8):1370-1380.
54. Koeffler HP:Peroxisome proliferator-activated receptor gamma and cancers. Clin Cancer Res 2003,9(1):1-9.
55. Tontonoz P, Hu E, Spiegelman BM:Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 1994, 79(7):1147-1156.
56. Tontonoz P, Singer S, Forman BM, Sarraf P, Fletcher JA, Fletcher CD, Brun RP, Mueller E, Altiok S, Oppenheim H et al: Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor gamma and the retinoid X receptor. Proc Natl Acad Sci U S A 1997, 94(1):237-241.
57. Demetri GD, Fletcher CD, Mueller E, Sarraf P, Naujoks R, Campbell N, Spiegelman BM, Singer S:Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci USA 1999,96(7):3951-3956.
58. HiRASe N, Yanase T, Mu Y, Muta K, Umemura T, Takayanagi R, Nawata H: Thiazolidinedione induces apoptosis and monocytic differentiation in the promyelocytic leukemia cell line HL60. Oncology 1999,57 Suppl 2:17-26.
59. Fujimura S, Suzumiya J, Nakamura K, Ono J:Effects of troglitazone on the growth and differentiation of hematopoietic cell lines. Int J Oncol 1998, 13(6):1263-1267.
60. Mangelsdorf DJ, Evans RM:The RXR heterodimers and orphan receptors. Cell 1995,83(6):841-850.
61. Wang T, Xu J, Yu X, Yang R, Han ZC:Peroxisome proliferator-activated receptor gamma in malignant diseases. Crit Rev Oncol Hematol 2006, 58(1):1-14.
62. Elstner E, Muller C, Koshizuka K, Williamson EA, Park D, Asou H, Shintaku P, Said JW, Heber D, Koeffler HP:Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc Natl Acad Sci USA 1998,95(15):8806-8811.
63. Zander T, Kraus JA, Grommes C, Schlegel U, Feinstein D, Klockgether T, Landreth G, Koenigsknecht J, Heneka MT:Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPARgamma. J Neurochem 2002,81(5):1052-1060.
64. Patel L, Pass I, Coxon P, Downes CP, Smith SA, Macphee CH:Tumor suppressor and anti-inflammatory actions of PPARgamma agonists are mediated via upregulation of PTEN. Curr Biol 2001, 11(10):764-768.
65. Pignatelli M, Cocca C, Santos A, Perez-Castillo A:Enhancement of BRCA1 gene expression by the peroxisome proliferator-activated receptor gamma in the MCF-7 breast cancer cell line. Oncogene 2003,22(35):5446-5450.
66. Yang K, Fan KH, Lamprecht SA, Edelmann W, Kopelovich L, Kucherlapati R, Lipkin M:Peroxisome proliferator-activated receptor gamma agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc1638 N/+ Mlhl+/- double mutant mice. Int J Cancer 2005,116(4):495-499.
67. Saez E, Rosenfeld J, Livolsi A, Olson P, Lombardo E, Nelson M, Banayo E,
Cardiff RD, Izpisua-Belmonte JC, Evans RM:PPAR gamma signaling exacerbates mammary gland tumor development. Genes Dev 2004, 18(5):528-540.
68. Metcalf D:Hematopoietic cytokines. Blood 2008,111(2):485-491.
69. Tenen DG:Disruption of differentiation in human cancer:AML shows the way. Nat Rev Cancer 2003,3(2):89-101.
70. Zhang DE, Zhang P, Wang ND, Hetherington CJ, Darlington GJ, Tenen DG: Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha-deficient mice. Proc Natl Acad Sci USA 1997,94(2):569-574.
71. Gombart AF, Hofrnann WK, Kawano S, Takeuchi S, Krug U, Kwok SH, Larsen RJ, Asou H, Miller CW, Hoelzer D et al: Mutations in the gene encoding the transcription factor CCAAT/enhancer binding protein alpha in myelodysplastic syndromes and acute myeloid leukemias. Blood 2002, 99(4):1332-1340.
72. Radomska HS, Huettner CS, Zhang P, Cheng T, Scadden DT, Tenen DG: CCAAT/enhancer binding protein alpha is a regulatory switch sufficient for induction of granulocytic development from bipotential myeloid progenitors. Mol Cell Biol 1998,18(7):4301-4314.
73. Tavor S, Park DJ, Gery S, Vuong PT, Gombart AF, Koeffler HP:Restoration of C/EBPalpha expression in a BCR-ABL+ cell line induces terminal granulocytic differentiation. J Biol Chem 2003,278(52):52651-52659.
74. Jones PA, Taylor SM:Cellular differentiation, cytidine analogs and DNA methylation. Cell 1980,20(1):85-93.
75. Kuendgen A, Gattermann N:Valproic acid for the treatment of myeloid malignancies. Cancer 2007,110(5):943-954.
76. Cimino G, Lo-Coco F, Fenu S, Travaglini L, Finolezzi E, Mancini M, Nanni M, Careddu A, Fazi F, Padula F et al: Sequential valproic acid/all-trans retinoic
acid treatment reprograms differentiation in refractory and high-risk acute myeloid leukemia. Cancer Res 2006,66(17):8903-8911.
77. Ciardiello F, Tortora G:EGFR antagonists in cancer treatment. N Engl J Med 2008,358(11):1160-1174.
78. Hanna J, Markoulaki S, Schorderet P, Carey BW, Beard C, Wernig M, Creyghton MP, Steine EJ, Cassady JP, Foreman R et al: Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 2008,133(2):250-264.
79. Yang J, Chai L, Gao C, Fowles TC, Alipio Z, Dang H, Xu D, Fink LM, Ward DC, Ma Y:SALL4 is a key regulator of survival and apoptosis in human leukemic cells. Blood 2008,112(3):805-813.
1. Bonnet D, Dick JE:Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997, 3(7):730-737.
2. Jordan CT:Unique molecular and cellular features of acute myelogenous leukemia stem cells. Leukemia 2002,16(4):559-562.
3. Blair A, Sutherland HJ:Primitive acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo lack surface expression of c-kit (CD117). Exp Hematol 2000,28(6):660-671.
4. Hosen N, Park CY, Tatsumi N, Oji Y, Sugiyama H, Gramatzki M, Krensky AM, Weissman IL:CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia. Proc Natl Acad Sci USA 2007,104(26):11008-11013.
5. van Rhenen A, van Dongen GA, Kelder A, Rombouts EJ, Feller N, Moshaver B, Stigter-van Walsum M, Zweegman S, Ossenkoppele GJ, Jan Schuurhuis G:The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. Blood 2007,110(7):2659-2666.
6. Hope KJ, Jin L, Dick JE:Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 2004,5(7):738-743.
7. Miyamoto T, Weissman IL, Akashi K:AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Natl Acad Sci USA 2000,97(13):7521-7526.
8. Huntly BJ, Shigematsu H, Deguchi K, Lee BH, Mizuno S, Duclos N, Rowan R, Amaral S, Curley D, Williams IR et al: MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 2004,6(6):587-596.
9. Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, Faber J, Levine JE, Wang J, Hahn WC, Gilliland DG et al: Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 2006, 442(7104):818-822.
10. Jamieson CH, Weissman IL, Passegue E:Chronic versus acute myelogenous leukemia:a question of self-renewal. Cancer Cell 2004,6(6):531-533.
11. Reya T, Clevers H:Wnt signalling in stem cells and cancer. Nature 2005, 434(7035):843-850.
12. Duncan AW, Rattis FM, DiMascio LN, Congdon KL, Pazianos G, Zhao C, Yoon K, Cock JM, Willert K, Gaiano N et al: Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 2005, 6(3):314-322.
13. Leong KG, Karsan A:Recent insights into the role of Notch signaling in tumorigenesis. Blood 2006,107(6):2223-2233.
14. Guzman ML, Swiderski CF, Howard DS, Grimes BA, Rossi RM, Szilvassy SJ, Jordan CT:Preferential induction of apoptosis for primary human leukemic stem cells. Proc Natl Acad Sci USA 2002,99(25):16220-16225.
15. Gilliland DG, Griffin JD:The roles of FLT3 in hematopoiesis and leukemia. Blood 2002,100(5):1532-1542.
16. Lessard J, Sauvageau G:Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 2003,423(6937):255-260.
17. Cozzio A, Passegue E, Ayton PM, Karsunky H, Cleary ML, Weissman IL: Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev 2003,17(24):3029-3035.
18. Dean M, Fojo T, Bates S:Tumour stem cells and drug resistance. Nat Rev Cancer 2005,5(4):275-284.
19. Ravandi F, Estrov Z:Eradication of leukemia stem cells as a new goal of therapy in leukemia. Clin Cancer Res 2006,12(2):340-344.
20. Hamann PR, Hinman LM, Beyer CF, Lindh D, Upeslacis J, Flowers DA, Bernstein I:An anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Choice of linker. Bioconjug Chem 2002, 13(1):40-46.
21. Bonnet D, Warren EH, Greenberg PD, Dick JE, Riddell SR:CD8(+) minor histocompatibility antigen-specific cytotoxic T lymphocyte clones eliminate human acute myeloid leukemia stem cells. Proc Natl Acad Sci U S A 1999, 96(15):8639-8644.
22. Xu Q, Simpson SE, Scialla TJ, Bagg A, Carroll M:Survival of acute myeloid leukemia cells requires PI3 kinase activation. Blood 2003,102(3):972-980.
2. Tsai PC, Fu TW, Chen YM, Ko TL, Chen TH, Shih YH, Hung SC, Fu YS:The therapeutic potential of human umbilical mesenchymal stem cells from Wharton's jelly in the treatment of rat liver fibrosis. Liver Transpl 2009, 15(5):484-495.
3. Liao W, Xie J, Zhong J, Liu Y, Du L, Zhou B, Xu J, Liu P, Yang S, Wang J et al: Therapeutic effect of human umbilical cord multipotent mesenchymal stromal cells in a rat model of stroke. Transplantation 2009,87(3):350-359.
4. Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S, Luo Y, Rao MS, Velagaleti G, Troyer D:Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease. Stem Cells 2006,24(3):781-792.
5. Friedman R, Betancur M, Boissel L, Tuncer H, Cetrulo C, Klingemann H: Umbilical cord mesenchymal stem cells:adjuvants for human cell transplantation. Biol Blood Marrow Transplant 2007,13(12):1477-1486.
6. Conget PA, Minguell JJ:Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 1999, 181(1):67-73.
7. Haynesworth SE, Baber MA, Caplan AI:Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro:effects of dexamethasone and IL-1 alpha. J Cell Physiol 1996,166(3):585-592.
8. Liu M, Yang SG, Shi L, Du WT, Liu PX, Xu J, Gu DS, Liang L, Dong CL, Han ZC:Mesenchymal stem cells from bone marrow show a stronger stimulating effect on megakaryocyte progenitor expansion than those from non-hematopoietic tissues. Platelets 2010,21(3):199-210.
9. Zhu Y, Sun Z, Han Q, Liao L, Wang J, Bian C, Li J, Yan X, Liu Y, Shao C et al: Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1. Leukemia 2009,23(5):925-933.
10. Filmus J, Buick RN:Relationship of c-myc expression to differentiation and proliferation of HL-60 cells. Cancer Res 1985,45(2):822-825.
11. Wallington LA, Durham J, Bunce CM, Brown G:Growth of single HL60 cells in liquid culture:analysis of the influences of differentiative agents. Leuk Res 1996,20(10):821-829.
12. Golomb HM, Rowley JD, Vardiman JW, Testa JR, Butler A:"Microgranular" acute promyelocytic leukemia:a distinct clinical, ultRAStructural, and cytogenetic entity. Blood 1980,55(2):253-259.
13. Tomonaga M, Yoshida Y, Tagawa M, Jinnai I, Kuriyama K, Amenomori T, Yoshioka A, Matsuo T, Nonaka H, Ichimaru M:Cytochemistry of acute promyelocytic leukemia (M3):leukemic promyelocytes exhibit heterogeneous patterns in cellular differentiation. Blood 1985, 66(2):350-357.
14. Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY:Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988,72(2):567-572.
15. Breitman TR, Selonick SE, Collins SJ:Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci USA 1980,77(5):2936-2940.
16. Nervi C, Ferrara FF, Fanelli M, Rippo MR, Tomassini B, Ferrucci PF, Ruthardt M, Gelmetti V, Gambacorti-Passerini C, Diverio D et al: Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion protein. Blood 1998,92(7):2244-2251.
17. Briquet A, Dubois S, Bekaert S, Dolhet M, Beguin Y, Gothot A:Prolonged ex vivo culture of human bone marrow mesenchymal stem cells influences their supportive activity toward NOD/SCID-repopulating cells and committed progenitor cells of B lymphoid and myeloid lineages. Haematologica,95(1):47-56.
1. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C:Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7). A report of the French-American-British Cooperative Group. Ann Intern Med 1985,103(3):460-462.
2. Minucci S, Pelicci PG:Determinants of oncogenic transformation in acute promyelocytic leukemia:the hetero-union makes the force. Cancer Cell 2007, 12(1):1-3.
3. Zhu J, Nasr R, Peres L, Riaucoux-Lormiere F, Honore N, Berthier C, Kamashev D, Zhou J, Vitoux D, Lavau C et al: RXR is an essential component of the oncogenic PML/RARA complex in vivo. Cancer Cell 2007,12(1):23-35.
4. Salomoni P, Pandolfi PP:The role of PML in tumor suppression. Cell 2002, 108(2):165-170.
5. Stone RM, Mayer RJ:The unique aspects of acute promyelocytic leukemia. J Clin Oncol 1990,8(11):1913-1921.
6. Kelly K, Cochran BH, Stiles CD, Leder P:Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell 1983,35(3 Pt 2):603-610.
7. Dalla-Favera R, Wong-Staal F, Gallo RC:Onc gene amplification in promyelocytic leukaemia cell line HL-60 and primary leukaemic cells of the same patient. Nature 1982,299(5878):61-63.
8. Grosso LE, Pitot HC:Transcriptional regulation of c-myc during chemically induced differentiation of HL-60 cultures. Cancer Res 1985,45(2):847-850.
9. Wolf D, Rotter V:Major deletions in the gene encoding the p53 tumor antigen cause lack of p53 expression in HL-60 cells. Proc Natl Acad Sci USA 1985,82(3):790-794.
10. Naharro G, Robbins KC, Reddy EP:Gene product of v-fgr one:hybrid
protein containing a portion of actin and a tyrosine-specific protein kinase. Science 1984,223(4631):63-66.
11. Gee CE, Griffin J, Sastre L, Miller LJ, Springer TA, Piwnica-Worms H, Roberts TM:Differentiation of myeloid cells is accompanied by increased levels of pp60c-src protein and kinase activity. Proc Natl Acad Sci U S A 1986, 83(14):5131-5135.
12. Sariban E, Mitchell T, Kufe D:Expression of the c-fms proto-oncogene during human monocytic differentiation. Nature 1985,316(6023):64-66.
13. Lanotte M, Martin-Thouvenin V, Najman S, Balerini P, Valensi F, Berger R: NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3). Blood 1991,77(5):1080-1086.
14. Hu ZB, Ma W, Uphoff CC, Lanotte M, Drexler HG:Modulation of gene expression in the acute promyelocytic leukemia cell line NB4. Leukemia 1993, 7(11):1817-1823.
15. Duprez E, Ruchaud S, Houge G, Martin-Thouvenin V, Valensi F, Kastner P, Berger R, Lanotte M:A retinoid acid 'resistant't(15;17) acute promyelocytic leukemia cell line:isolation, morphological, immunological, and molecular features. Leukemia 1992,6(12):1281-1287.
16. Dermime S, Grignani F, Clerici M, Nervi C, Sozzi G, Talamo GP, Marchesi E, Formelli F, Parmiani G, Pelicci PG et al: Occurrence of resistance to retinoic acid in the acute promyelocytic leukemia cell line NB4 is associated with altered expression of the pml/RAR alpha protein. Blood 1993, 82(5):1573-1577.
17. Fibach E, Hayashi M, Sachs L:Control of normal differentiation of myeloid leukemic cells to macrophages and granulocytes. Proc Natl Acad Sci U S A 1973,70(2):343-346.
18. Paran M, Sachs L, Barak Y, Resnitzky P:In vitro induction of granulocyte differentiation in hematopoietic cells from leukemic and non-leukemic
patients. Proc Natl Acad Sci USA 1970,67(3):1542-1549.
19. Breitman TR, Selonick SE, Collins SJ:Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci USA 1980,77(5):2936-2940.
20. Breitman TR, Collins SJ, Keene BR:Terminal differentiation of human promyelocytic leukemic cells in primary culture in response to retinoic acid. Blood 1981,57(6):1000-1004.
21. Runde V, Aul C, Sudhoff T, Heyll A, Schneider W:Retinoic acid in the treatment of acute promyelocytic leukemia:inefficacy of the 13-cis isomer and induction of complete remission by the all-trans isomer complicated by thromboembolic events. Ann Hematol 1992,64(6):270-272.
22. Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY:Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988,72(2):567-572.
23. Wang ZY:Ham-Wasserman lecture:treatment of acute leukemia by inducing differentiation and apoptosis. Hematology Am Soc Hematol Educ Program 2003:1-13.
24. Collins SJ:Retinoic acid receptors, hematopoiesis and leukemogenesis. Curr Opin Hematol 2008,15(4):346-351.
25. Wang ZY, Chen Z:Acute promyelocytic leukemia:from highly fatal to highly curable. Blood 2008,111(5):2505-2515.
26. Scaglioni PP, Pandolfi PP:The theory of APL revisited. Curr Top Microbiol Immunol.2007,313:85-100.
27. Zheng PZ, Wang KK, Zhang QY, Huang QH, Du YZ, Zhang QH, Xiao DK, Shen SH, Imbeaud S, Eveno E et al: Systems analysis of transcriptome and proteome in retinoic acid/arsenic trioxide-induced cell differentiation/apoptosis of promyelocytic leukemia. Proc Natl Acad Sci U S A 2005,102(21):7653-7658.
28. Park DJ, Vuong PT, de Vos S, Douer D, Koeffler HP:Comparative analysis of genes regulated by PML/RAR alpha and PLZF/RAR alpha in response to retinoic acid using oligonucleotide arrays. Blood 2003,102(10):3727-3736.
29. Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, Zhu J, Tang W, Sun GL, Yang KQ et al: Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL):Ⅱ. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 1997,89(9):3354-3360.
30. Lu DP, Qiu JY, Jiang B, Wang Q, Liu KY, Liu YR, Chen SS:Tetra-arsenic tetra-sulfide for the treatment of acute promyelocytic leukemia:a pilot report. Blood 2002,99(9):3136-3143.
31. Chen GQ, Shi XG, Tang W, Xiong SM, Zhu J, Cai X, Han ZG, Ni JH, Shi GY, Jia PM et al: Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL):Ⅰ. As2O3 exerts dose-dependent dual effects on APL cells. Blood 1997,89(9):3345-3353.
32. Matsui W, Smith BD, Vala M, Beal N, Huff CA, Diehl LF, Jones RJ: Requirement for myeloid growth factors in the differentiation of acute promyelocytic leukaemia. Br JHaematol 2005,128(6):853-862.
33. Kakizuka A, Miller WH, Jr., Umesono K, Warrell RP, Jr., Frankel SR, Murty VV, Dmitrovsky E, Evans RM:Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell 1991,66(4):663-674.
34. Melnick A, Licht JD:Deconstructing a disease:RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood 1999,93(10):3167-3215.
35. Shih LY, Kuo MC, Liang DC, Huang CF, Lin TL, Wu JH, Wang PN, Dunn P, Lai CL:Internal tandem duplication and Asp835 mutations of the FMS-like tyrosine kinase 3 (FLT3) gene in acute promyelocytic leukemia. Cancer 2003, 98(6):1206-1216.
36. Nervi C, Ferrara FF, Fanelli M, Rippo MR, Tomassini B, Ferrucci PF, Ruthardt M, Gelmetti V, Gambacorti-Passerini C, Diverio D et al: Caspases mediate retinoic acid-induced degradation of the acute promyelocytic leukemia PML/RARalpha fusion protein. Blood 1998,92(7):2244-2251.
37. Zhu J, Gianni M, Kopf E, Honore N, Chelbi-Alix M, Koken M, Quignon F, Rochette-Egly C, de The H:Retinoic acid induces proteasome-dependent degradation of retinoic acid receptor alpha (RARalpha) and oncogenic RARalpha fusion proteins. Proc Natl Acad Sci U S A 1999, 96(26):14807-14812.
38. Lallemand-Breitenbach V, Zhu J, Puvion F, Koken M, Honore N, Doubeikovsky A, Duprez E, Pandolfi PP, Puvion E, Freemont P et al: Role of promyelocytic leukemia (PML) sumolation in nuclear body formation, 11S proteasome recruitment, and As2O3-induced PML or PML/retinoic acid receptor alpha degradation. J Exp Med 2001,193(12):1361-1371.
39. Muller S, Matunis MJ, Dejean A:Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleus. Embo J 1998,17(1):61-70.
40. Kamashev D, Vitoux D, De The H:PML-RARA-RXR oligomers mediate retinoid and rexinoid/cAMP cross-talk in acute promyelocytic leukemia cell differentiation. JExp Med 2004,199(8):1163-1174.
41. Liu TX, Zhang JW, Tao J, Zhang RB, Zhang QH, Zhao CJ, Tong JH, Lanotte M, Waxman S, Chen SJ et al: Gene expression networks underlying retinoic acid-induced differentiation of acute promyelocytic leukemia cells. Blood 2000,96(4):1496-1504.
42. Rocca B, Morosetti R, Habib A, Maggiano N, Zassadowski F, Ciabattoni G, Chomienne C, Papp B, Ranelletti FO:Cyclooxygenase-1, but not -2, is upregulated in NB4 leukemic cells and human primary promyelocytic blasts during differentiation. Leukemia 2004,18(8):1373-1379.
43. Kini AR, Peterson LA, Tallman MS, Lingen MW:Angiogenesis in acute promyelocytic leukemia:induction by vascular endothelial growth factor and inhibition by all-trans retinoic acid. Blood 2001,97(12):3919-3924.
44. Zhu J, Guo WM, Yao YY, Zhao WL, Pan L, Cai X, Ju B, Sun GL, Wang HL, Chen SJ et al: Tissue factors on acute promyelocytic leukemia and endothelial cells are differently regulated by retinoic acid, arsenic trioxide and chemotherapeutic agents. Leukemia 1999,13(7):1062-1070.
45. Pendino F, Flexor M, Delhommeau F, Buet D, Lanotte M, Segal-Bendirdjian E: Retinoids down-regulate telomeRASe and telomere length in a pathway distinct from leukemia cell differentiation. Proc Natl Acad Sci U S A 2001, 98(12):6662-6667.
46. Tarkanyi I, Dudognon C, Hillion J, Pendino F, Lanotte M, Aradi J, Segal-Bendirdjian E:Retinoid/arsenic combination therapy of promyelocytic leukemia:induction of telomeRASe-dependent cell death. Leukemia 2005, 19(10):1806-1811.
47. Tarrade A, Bastien J, Bruck N, Bauer A, Gianni M, Rochette-Egly C:Retinoic acid and arsenic trioxide cooperate for apoptosis through phosphorylated RXR alpha. Oncogene 2005,24(14):2277-2288.
48. Zhu J, Lallemand-Breitenbach V, de The H:Pathways of retinoic acid- or arsenic trioxide-induced PML/RARalpha catabolism, role of oncogene degradation in disease remission. Oncogene 2001,20(49):7257-7265.
49. Zhao Q, Tao J, Zhu Q, Jia PM, Dou AX, Li X, Cheng F, Waxman S, Chen GQ, Chen SJ et al:Rapid induction of cAMP/PKA pathway during retinoic acid-induced acute promyelocytic leukemia cell differentiation. Leukemia 2004,18(2):285-292.
50. Leung J, Pang A, Yuen WH, Kwong YL, Tse EW:Relationship of expression of aquaglyceroporin 9 with arsenic uptake and sensitivity in leukemia cells. Blood 2007,109(2):740-746.
51. Liu M, Lee MH, Cohen M, Bommakanti M, Freedman LP:Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev 1996, 10(2):142-153.
52. Verlinden L, Verstuyf A, Convents R, Marcelis S, Van Camp M, Bouillon R: Action of 1,25(OH)2D3 on the cell cycle genes, cyclin D1, p21 and p27 in MCF-7 cells. Mol Cell Endocrinol 1998,142(1-2):57-65.
53. Jensen SS, Madsen MW, Lukas J, Binderup L, Bartek J:Inhibitory effects of lalpha,25-dihydroxyvitamin D(3) on the G(1)-S phase-controlling machinery. Mol Endocrinol 2001,15(8):1370-1380.
54. Koeffler HP:Peroxisome proliferator-activated receptor gamma and cancers. Clin Cancer Res 2003,9(1):1-9.
55. Tontonoz P, Hu E, Spiegelman BM:Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 1994, 79(7):1147-1156.
56. Tontonoz P, Singer S, Forman BM, Sarraf P, Fletcher JA, Fletcher CD, Brun RP, Mueller E, Altiok S, Oppenheim H et al: Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor gamma and the retinoid X receptor. Proc Natl Acad Sci U S A 1997, 94(1):237-241.
57. Demetri GD, Fletcher CD, Mueller E, Sarraf P, Naujoks R, Campbell N, Spiegelman BM, Singer S:Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci USA 1999,96(7):3951-3956.
58. HiRASe N, Yanase T, Mu Y, Muta K, Umemura T, Takayanagi R, Nawata H: Thiazolidinedione induces apoptosis and monocytic differentiation in the promyelocytic leukemia cell line HL60. Oncology 1999,57 Suppl 2:17-26.
59. Fujimura S, Suzumiya J, Nakamura K, Ono J:Effects of troglitazone on the growth and differentiation of hematopoietic cell lines. Int J Oncol 1998, 13(6):1263-1267.
60. Mangelsdorf DJ, Evans RM:The RXR heterodimers and orphan receptors. Cell 1995,83(6):841-850.
61. Wang T, Xu J, Yu X, Yang R, Han ZC:Peroxisome proliferator-activated receptor gamma in malignant diseases. Crit Rev Oncol Hematol 2006, 58(1):1-14.
62. Elstner E, Muller C, Koshizuka K, Williamson EA, Park D, Asou H, Shintaku P, Said JW, Heber D, Koeffler HP:Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc Natl Acad Sci USA 1998,95(15):8806-8811.
63. Zander T, Kraus JA, Grommes C, Schlegel U, Feinstein D, Klockgether T, Landreth G, Koenigsknecht J, Heneka MT:Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPARgamma. J Neurochem 2002,81(5):1052-1060.
64. Patel L, Pass I, Coxon P, Downes CP, Smith SA, Macphee CH:Tumor suppressor and anti-inflammatory actions of PPARgamma agonists are mediated via upregulation of PTEN. Curr Biol 2001, 11(10):764-768.
65. Pignatelli M, Cocca C, Santos A, Perez-Castillo A:Enhancement of BRCA1 gene expression by the peroxisome proliferator-activated receptor gamma in the MCF-7 breast cancer cell line. Oncogene 2003,22(35):5446-5450.
66. Yang K, Fan KH, Lamprecht SA, Edelmann W, Kopelovich L, Kucherlapati R, Lipkin M:Peroxisome proliferator-activated receptor gamma agonist troglitazone induces colon tumors in normal C57BL/6J mice and enhances colonic carcinogenesis in Apc1638 N/+ Mlhl+/- double mutant mice. Int J Cancer 2005,116(4):495-499.
67. Saez E, Rosenfeld J, Livolsi A, Olson P, Lombardo E, Nelson M, Banayo E,
Cardiff RD, Izpisua-Belmonte JC, Evans RM:PPAR gamma signaling exacerbates mammary gland tumor development. Genes Dev 2004, 18(5):528-540.
68. Metcalf D:Hematopoietic cytokines. Blood 2008,111(2):485-491.
69. Tenen DG:Disruption of differentiation in human cancer:AML shows the way. Nat Rev Cancer 2003,3(2):89-101.
70. Zhang DE, Zhang P, Wang ND, Hetherington CJ, Darlington GJ, Tenen DG: Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha-deficient mice. Proc Natl Acad Sci USA 1997,94(2):569-574.
71. Gombart AF, Hofrnann WK, Kawano S, Takeuchi S, Krug U, Kwok SH, Larsen RJ, Asou H, Miller CW, Hoelzer D et al: Mutations in the gene encoding the transcription factor CCAAT/enhancer binding protein alpha in myelodysplastic syndromes and acute myeloid leukemias. Blood 2002, 99(4):1332-1340.
72. Radomska HS, Huettner CS, Zhang P, Cheng T, Scadden DT, Tenen DG: CCAAT/enhancer binding protein alpha is a regulatory switch sufficient for induction of granulocytic development from bipotential myeloid progenitors. Mol Cell Biol 1998,18(7):4301-4314.
73. Tavor S, Park DJ, Gery S, Vuong PT, Gombart AF, Koeffler HP:Restoration of C/EBPalpha expression in a BCR-ABL+ cell line induces terminal granulocytic differentiation. J Biol Chem 2003,278(52):52651-52659.
74. Jones PA, Taylor SM:Cellular differentiation, cytidine analogs and DNA methylation. Cell 1980,20(1):85-93.
75. Kuendgen A, Gattermann N:Valproic acid for the treatment of myeloid malignancies. Cancer 2007,110(5):943-954.
76. Cimino G, Lo-Coco F, Fenu S, Travaglini L, Finolezzi E, Mancini M, Nanni M, Careddu A, Fazi F, Padula F et al: Sequential valproic acid/all-trans retinoic
acid treatment reprograms differentiation in refractory and high-risk acute myeloid leukemia. Cancer Res 2006,66(17):8903-8911.
77. Ciardiello F, Tortora G:EGFR antagonists in cancer treatment. N Engl J Med 2008,358(11):1160-1174.
78. Hanna J, Markoulaki S, Schorderet P, Carey BW, Beard C, Wernig M, Creyghton MP, Steine EJ, Cassady JP, Foreman R et al: Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 2008,133(2):250-264.
79. Yang J, Chai L, Gao C, Fowles TC, Alipio Z, Dang H, Xu D, Fink LM, Ward DC, Ma Y:SALL4 is a key regulator of survival and apoptosis in human leukemic cells. Blood 2008,112(3):805-813.
1. Bonnet D, Dick JE:Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 1997, 3(7):730-737.
2. Jordan CT:Unique molecular and cellular features of acute myelogenous leukemia stem cells. Leukemia 2002,16(4):559-562.
3. Blair A, Sutherland HJ:Primitive acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo lack surface expression of c-kit (CD117). Exp Hematol 2000,28(6):660-671.
4. Hosen N, Park CY, Tatsumi N, Oji Y, Sugiyama H, Gramatzki M, Krensky AM, Weissman IL:CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia. Proc Natl Acad Sci USA 2007,104(26):11008-11013.
5. van Rhenen A, van Dongen GA, Kelder A, Rombouts EJ, Feller N, Moshaver B, Stigter-van Walsum M, Zweegman S, Ossenkoppele GJ, Jan Schuurhuis G:The novel AML stem cell associated antigen CLL-1 aids in discrimination between normal and leukemic stem cells. Blood 2007,110(7):2659-2666.
6. Hope KJ, Jin L, Dick JE:Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol 2004,5(7):738-743.
7. Miyamoto T, Weissman IL, Akashi K:AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Natl Acad Sci USA 2000,97(13):7521-7526.
8. Huntly BJ, Shigematsu H, Deguchi K, Lee BH, Mizuno S, Duclos N, Rowan R, Amaral S, Curley D, Williams IR et al: MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 2004,6(6):587-596.
9. Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, Faber J, Levine JE, Wang J, Hahn WC, Gilliland DG et al: Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature 2006, 442(7104):818-822.
10. Jamieson CH, Weissman IL, Passegue E:Chronic versus acute myelogenous leukemia:a question of self-renewal. Cancer Cell 2004,6(6):531-533.
11. Reya T, Clevers H:Wnt signalling in stem cells and cancer. Nature 2005, 434(7035):843-850.
12. Duncan AW, Rattis FM, DiMascio LN, Congdon KL, Pazianos G, Zhao C, Yoon K, Cock JM, Willert K, Gaiano N et al: Integration of Notch and Wnt signaling in hematopoietic stem cell maintenance. Nat Immunol 2005, 6(3):314-322.
13. Leong KG, Karsan A:Recent insights into the role of Notch signaling in tumorigenesis. Blood 2006,107(6):2223-2233.
14. Guzman ML, Swiderski CF, Howard DS, Grimes BA, Rossi RM, Szilvassy SJ, Jordan CT:Preferential induction of apoptosis for primary human leukemic stem cells. Proc Natl Acad Sci USA 2002,99(25):16220-16225.
15. Gilliland DG, Griffin JD:The roles of FLT3 in hematopoiesis and leukemia. Blood 2002,100(5):1532-1542.
16. Lessard J, Sauvageau G:Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 2003,423(6937):255-260.
17. Cozzio A, Passegue E, Ayton PM, Karsunky H, Cleary ML, Weissman IL: Similar MLL-associated leukemias arising from self-renewing stem cells and short-lived myeloid progenitors. Genes Dev 2003,17(24):3029-3035.
18. Dean M, Fojo T, Bates S:Tumour stem cells and drug resistance. Nat Rev Cancer 2005,5(4):275-284.
19. Ravandi F, Estrov Z:Eradication of leukemia stem cells as a new goal of therapy in leukemia. Clin Cancer Res 2006,12(2):340-344.
20. Hamann PR, Hinman LM, Beyer CF, Lindh D, Upeslacis J, Flowers DA, Bernstein I:An anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Choice of linker. Bioconjug Chem 2002, 13(1):40-46.
21. Bonnet D, Warren EH, Greenberg PD, Dick JE, Riddell SR:CD8(+) minor histocompatibility antigen-specific cytotoxic T lymphocyte clones eliminate human acute myeloid leukemia stem cells. Proc Natl Acad Sci U S A 1999, 96(15):8639-8644.
22. Xu Q, Simpson SE, Scialla TJ, Bagg A, Carroll M:Survival of acute myeloid leukemia cells requires PI3 kinase activation. Blood 2003,102(3):972-980.