| |
FLT3 expression and IL10 promoter polymorphism in acute myeloid leukemia with RUNX1-RUNX1T1
- 作者：Myungshin Kim ; Jiyeon Kim ; Jung Rok Kim ; Eunhee Han…
- 关键词：FLT3 expression ; RUNX1 mutation ; IL10 promoter polymorphism ; Acute myeloid leukemia
- 刊名：Molecular Biology Reports
- 出版年：2015
- 出版时间：February 2015
- 年：2015
- 卷：42
- 期：2
- 页码：451-456
- 全文大小：566 KB
- 参考文献：1. Gilliland DG, Griffin JD (2002) The roles of FLT3 in hematopoiesis and leukemia. Blood 100(5):1532-542. doi:10.1182/blood-2002-02-0492 CrossRef
2. Stirewalt DL, Radich JP (2003) The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer 3(9):650-65. doi:10.1038/nrc1169 CrossRef
3. Kindler T, Lipka DB, Fischer T (2010) FLT3 as a therapeutic target in AML: still challenging after all these years. Blood 116(24):5089-102. doi:10.1182/blood-2010-04-261867 CrossRef
4. Ozeki K, Kiyoi H, Hirose Y, Iwai M, Ninomiya M, Kodera Y, Miyawaki S, Kuriyama K, Shimazaki C, Akiyama H, Nishimura M, Motoji T, Shinagawa K, Takeshita A, Ueda R, Ohno R, Emi N, Naoe T (2004) Biologic and clinical significance of the FLT3 transcript level in acute myeloid leukemia. Blood 103(5):1901-908. doi:10.1182/blood-2003-06-1845 CrossRef
5. Silva FP, Lind A, Brouwer-Mandema G, Valk PJ, Giphart-Gassler M (2007) Trisomy 13 correlates with RUNX1 mutation and increased FLT3 expression in AML-M0 patients. Haematologica 92(8):1123-126 CrossRef
6. Dicker F, Haferlach C, Kern W, Haferlach T, Schnittger S (2007) Trisomy 13 is strongly associated with AML1/RUNX1 mutations and increased FLT3 expression in acute myeloid leukemia. Blood 110(4):1308-316. doi:10.1182/blood-2007-02-072595 CrossRef
7. Baldwin BR, Li L, Tse KF, Small S, Collector M, Whartenby KA, Sharkis SJ, Racke F, Huso D, Small D (2007) Transgenic mice expressing Tel-FLT3, a constitutively activated form of FLT3, develop myeloproliferative disease. Leukemia 21(4):764-71. doi:10.1038/sj.leu.2404532
8. de Deus DM, de Souza PR, Muniz MT (2013) High FLT3 expression and IL10 (G1082A) polymorphism in poor overall survival in calla acute lymphoblastic leukemia. Mol Biol Rep 40(2):1609-613. doi:10.1007/s11033-012-2209-4 CrossRef
9. Mangan JK, Speck NA (2011) RUNX1 mutations in clonal myeloid disorders: from conventional cytogenetics to next generation sequencing, a story 40?years in the making. Crit Rev Oncog 16(1-):77-1 CrossRef
10. Zhang B, Ho YW, Huang Q, Maeda T, Lin A, Lee SU, Hair A, Holyoake TL, Huettner C, Bhatia R (2012) Altered microenvironmental regulation of leukemic and normal stem cells in chronic myelogenous leukemia. Cancer Cell 21(4):577-92. doi:10.1016/j.ccr.2012.02.018 CrossRef
11. Arber DA, Brunning RD, Le Beau MM, Falini B, Vardiman JW, Porwit A, Thiele J, Bloomfield CD (2008) Acute myeloid leukaemia with recurrent genetic abnormalities. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon, pp 110-12
12. Kuchenbauer F, Kern W, Schoch C, Kohlmann A, Hiddemann W, Haferlach T, Schnittger S (2005) Detailed analysis of FLT3 expression levels in acute myeloid leukemia. Haematologica 90(12):1617-625
13. Vora HH, Shukla SN, Brahambhatt BV, Mehta SH, Patel NA, Parikh SK, Shah KN, Shah PM (2010) Clinical relevance of FLT3 receptor protein expression in Indian patients with acute leukemia. Asia-Pac J Clin oncol 6(4):306-19. doi:10.1111/j.1743-7563.2010.01322.x CrossRef
14. Grunwald MR, Levis MJ (2013) FLT3 inhibitors for acute myeloid leukemia: a review of their efficacy and mechanisms of resistance. Int J Hematol 97(6):683-94. doi:10.1007/s12185-013-1334-8
文摘
We investigated the correlation between FLT3 expression and IL10 gene promoter polymorphism in acute myeloid leukemia with RUNX1-RUNX1T1 and their clinical significance. FLT3 mRNA expression was measured by real-time quantitative PCR (qPCR) and immunohistochemical staining (IHC) on bone marrow (BM) leukemic cells. IL10 gene promoter polymorphisms including rs1800896 (G-1082A), rs1800871 (C-819T), and rs1800872 (C-592T) were genotyped by direct sequencing. Among 45 enrolled patients, 32 (71.1?%) exhibited FLT3 overexpression, whose FLT3 mRNA level was higher than normal cut-off value (0.02). The IHC results also consisted with FLT3 mRNA expression data achieved by qPCR. The FLT3 mRNA level was significantly different among 3 IHC staining groups (P?FLT3 expression level was correlated with the percentage of BM CD34 positive cells (R?=?0.360, P?=?0.016). The elevated FLT3 expression at initial BM were decreased after remission and maintained lower than the cut-off level. FLT3 expression was not dependent on IL10 gene promoter polymorphisms. FLT3 overexpression itself did not demonstrate significant effects on overall survival (OS). However, it is notable that IL10 rs1800896 GA genotype tended to have a lower estimated mean OS (20.1?months) compared to GG genotype (54.6?months), but the statistical significance was not derived because of limited number of patients in this study (P?=?0.072). Further studies including more type of leukemia and patients may be helpful to understand the relations between cytokine genotype and FLT3 expression and their prognostic impact.
| |
NGLC 2004-2010.National Geological Library of China All Rights Reserved.
Add:29 Xueyuan Rd,Haidian District,Beijing,PRC. Mail Add: 8324 mailbox 100083
For exchange or info please contact us via email.
| |
