移植前高血清铁蛋白对急性髓系白血病及骨髓增生异常综合征预后影响研究新进展
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摘要
<正>铁过载是体内铁含量增高,通过诱导产生活性氧继而导致机体内多种脏器损伤的一种病理状态。过多的铁沉积在不同的组织器官中,不仅影响机体基础疾病的进展,而且影响患者的预后。血清铁蛋白(serum ferritin,SF)评价体内铁过载(SF>1 000ng/ml)程度的特异性较差,是由于急性感染、炎症及恶性肿瘤亦会影响机体SF水平。近年来有多篇
Iron overload,apathological state,is the body's iron stores up-regulated,which could cause damages occurred in many organs through the production of reactive oxygen species.Iron deposition in various organs,which not only affects the prognosis of patients but also might influence the progression of the underlying diseases.Serum ferritin(SF)has a limited specificity in terms of assessing the extent of the iron overload(defined as SF>1 000 ng/ml),because the SF levels can be influenced by the acute infection,inflammation and malignancies.Many researches have recently proved that the elevated SF prior to allogeneic hematopoietic stem cell transplantation(allo-HSCT)have a negative impact on the prognosis of patients with acute myeloid leukemia(AML)and myelodysplastic syndrome(MDS).However,the clinical cut-off value of pre-tranplantation elevated SF associated with the poor prognosis of AML and MDS patients undergoing allo-HSCT ranging from 500 to 2 500 ng/ml,varied considerably.We comprehensively searched the China National Knowledge Infrastructure,PubMed and Web of Science,with the purpose of systematic reviewing the latest progress of researches focused on investigating the prognostic role of pre-transplantation elevated SF in patients with MDS and AML who underwent allo-HSCT.
Iron overload,apathological state,is the body's iron stores up-regulated,which could cause damages occurred in many organs through the production of reactive oxygen species.Iron deposition in various organs,which not only affects the prognosis of patients but also might influence the progression of the underlying diseases.Serum ferritin(SF)has a limited specificity in terms of assessing the extent of the iron overload(defined as SF>1 000 ng/ml),because the SF levels can be influenced by the acute infection,inflammation and malignancies.Many researches have recently proved that the elevated SF prior to allogeneic hematopoietic stem cell transplantation(allo-HSCT)have a negative impact on the prognosis of patients with acute myeloid leukemia(AML)and myelodysplastic syndrome(MDS).However,the clinical cut-off value of pre-tranplantation elevated SF associated with the poor prognosis of AML and MDS patients undergoing allo-HSCT ranging from 500 to 2 500 ng/ml,varied considerably.We comprehensively searched the China National Knowledge Infrastructure,PubMed and Web of Science,with the purpose of systematic reviewing the latest progress of researches focused on investigating the prognostic role of pre-transplantation elevated SF in patients with MDS and AML who underwent allo-HSCT.
引文
[1]Wang J,Pantopoulos K.Regulation of cellular iron metabolism[J].Biochem J,2011,434:365-381.
[2]Papanikolaou G,Pantopoulos K.Systemic iron homeostasis and erythropoiesis[J].IUBMB Life,2017,69:399-413.
[3]Yanatori I,Kishi F.DMT1and iron transport[J].Free Radic Biol Med,2019,133:55-63.
[4]Moukalled NM,El Rassi FA,Temraz SN,et al.Iron overload in patients with myelodysplastic syndromes:An updated overview[J].Cancer,2018,124:3979-3989.
[5]Nemeth E,Tuttle MS,Powelson J,et al.Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization[J].Science,2004,306:2090-2093.
[6]Winter WE,Bazydlo LA,Harris NS.The molecular biology of human iron metabolism[J].Lab Med,2014,45:92-102.
[7]Babitt JL,Huang FW,Wrighting DM,et al.Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression[J].Nat Genet,2006,38:531-539.
[8]Niederkofler V,Salie R,Arber S.Hemojuvelin is essential for dietary iron sensing,and its mutation leads to severe iron overload[J].J Clin Invest,2005,115:2180-2186.
[9]Silvestri L,Pagani A,Nai A,et al.The serine protease matriptase-2(TMPRSS6)inhibits hepcidin activation by cleaving membrane hemojuvelin[J].Cell Metab,2008,8:502-511.
[10]Kautz L,Jung G,Valore EV,et al.Identification of erythroferrone as an erythroid regulator of iron metabolism[J].Nat Genet,2014,46:678-684.
[11]Tanno T,Porayette P,Sripichai O,et al.Identification of TWSG1as a second novel erythroid regulator of hepcidin expression in murine and human cells[J].Blood,2009,114:181-186.
[12]Shah YM,Matsubara T,Ito S,et al.Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency[J].Cell Metab,2009,9:152-164.
[13]Rishi G,Wallace DF,Subramaniam VN.Hepcidin:regulation of the master iron regulator[J].Biosci Rep,2015,35:e00192.
[14]Delaby C,Pilard N,Puy H,et al.Sequential regulation of ferroportin expression after erythrophagocytosis in murine macrophages:early mRNA induction by haem,followed by iron-dependent protein expression[J].Biochem J,2008,411:123-131.
[15]Italia K,Colah R,Ghosh K.Experimental animal model to study iron overload and iron chelation and review of other such models[J].Blood Cells Mol Dis,2015,55:194-199.
[16]Porter JB,de Witte T,Cappellini MD,et al.New insights into transfusion-related iron toxicity:Implications for the oncologist[J].Crit Rev Oncol Hematol,2016,99:261-271.
[17]Cabantchik ZI,Breuer W,Zanninelli G,et al.LPI-labile plasma iron in iron overload[J].Best Pract Res Clin Haematol,2005,18:277-287.
[18]Zuo Y,Xiang B,Yang J,et al.Oxidative modification of caspase-9facilitates its activation via disulfide-mediated interaction with Apaf-1[J].Cell Res,2009,19:449-457.
[19]Alessandrino EP,Della Porta MG,Bacigalupo A,et al.Prognostic impact of pre-transplantation transfusion history and secondary iron overload in patients with myelodysplastic syndrome undergoing allogeneic stem cell transplantation:a GITMO study[J].Haematologica,2010,95:476-484.
[20]Tachibana T,Tanaka M,Takasaki H,et al.Pretransplant serum ferritin is associated with bloodstream infections within 100days of allogeneic stem cell transplantation for myeloid malignancies[J].Int J Hematol,2011,93:368-374.
[21]Jacobi N,Herich L.Measurement of liver iron concentration by superconducting quantum interference device biomagnetic liver susceptometry validates serum ferritin as prognostic parameter for allogeneic stem cell transplantation[J].Eur J Haematol,2016,97:336-341.
[22]Anderson LJ.Assessment of iron overload with T2*magnetic resonance imaging[J].Prog Cardiovasc Dis,2011,54:287-294.
[23]Dohner H,Estey E,Grimwade D,et al.Diagnosis and management of AML in adults:2017ELN recommendations from an international expert panel[J].Blood,2017,129:424-447.
[24]Tachibana T,Tanaka M,Yamazaki E,et al.Multicenter validation of scoring system of pre-transplant serum ferritin and disease risk in patients with acute myeloid leukemia and myelodysplastic syndrome after allogeneic hematopoietic stem cell transplant[J].Leuk Lymphoma,2013,54:1318-1320.
[25]Finke J,Schmoor C,Bertz H,et al.Long-term followup of therapy-related myelodysplasia and AML patients treated with allogeneic hematopoietic cell transplantation[J].Bone Marrow Transplant,2016,51:771-777.
[26]Boehm A,Sperr WR,Kalhs P,et al.Long-term followup after allogeneic stem cell transplantation in patients with myelodysplastic syndromes or secondary acute myeloid leukemia:a single center experience[J].Wien Klin Wochenschr,2014,126:23-29.
[27]Atilla E,Toprak SK,Demirer T.Current review of iron overload and related complications in hematopoietic stem cell transplantation[J].Turk J Haematol,2017,34:1-9.
[28]Kim YR,Kim JS,Cheong JW,et al.Transfusion-associated iron overload as an adverse risk factor for transplantation outcome in patients undergoing reduced-intensity stem cell transplantation for myeloid malignancies[J].Acta Haematol,2008,120:182-189.
[29]Komrokji RS,Corrales-Yepez M,Kharfan-Dabaja MA,et al.Hypoalbuminemia is an independent prognostic factor for overall survival in myelodysplastic syndromes[J].Am J Hematol,2012,87:1006-1009.
[30]Jang JE,Kim SJ,Cheong JW,et al.Early CMV replication and subsequent chronic GVHD have a significant anti-leukemic effect after allogeneic HSCT in acute myeloid leukemia[J].Ann Hematol,2015,94:275-282.
[31]Lim ZY,Fiaccadori V,Gandhi S,et al.Impact of pretransplant serum ferritin on outcomes of patients with myelodysplastic syndromes or secondary acute myeloid leukaemia receiving reduced intensity conditioning allogeneic haematopoietic stem cell transplantation[J].Leuk Res,2010,34:723-727.
[32]Artz AS,Logan B,Zhu X,et al.The prognostic value of serum C-reactive protein,ferritin,and albumin prior to allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndromes[J].Haematologica,2016,101:1426-1433.
[33]Yan Z,Chen X,Wang H,et al.Effect of pre-transplantation serum ferritin on outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation:A meta-analysis[J].Medicine(Baltimore),2018,97:e10310.
[34]Pileggi C,Di Sanzo M,Mascaro V,et al.Role of serum ferritin level on overall survival in patients with myelodysplastic syndromes:Results of a meta-analysis of observational studies[J].PLoS One,2017,12:e0179016.
[2]Papanikolaou G,Pantopoulos K.Systemic iron homeostasis and erythropoiesis[J].IUBMB Life,2017,69:399-413.
[3]Yanatori I,Kishi F.DMT1and iron transport[J].Free Radic Biol Med,2019,133:55-63.
[4]Moukalled NM,El Rassi FA,Temraz SN,et al.Iron overload in patients with myelodysplastic syndromes:An updated overview[J].Cancer,2018,124:3979-3989.
[5]Nemeth E,Tuttle MS,Powelson J,et al.Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization[J].Science,2004,306:2090-2093.
[6]Winter WE,Bazydlo LA,Harris NS.The molecular biology of human iron metabolism[J].Lab Med,2014,45:92-102.
[7]Babitt JL,Huang FW,Wrighting DM,et al.Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression[J].Nat Genet,2006,38:531-539.
[8]Niederkofler V,Salie R,Arber S.Hemojuvelin is essential for dietary iron sensing,and its mutation leads to severe iron overload[J].J Clin Invest,2005,115:2180-2186.
[9]Silvestri L,Pagani A,Nai A,et al.The serine protease matriptase-2(TMPRSS6)inhibits hepcidin activation by cleaving membrane hemojuvelin[J].Cell Metab,2008,8:502-511.
[10]Kautz L,Jung G,Valore EV,et al.Identification of erythroferrone as an erythroid regulator of iron metabolism[J].Nat Genet,2014,46:678-684.
[11]Tanno T,Porayette P,Sripichai O,et al.Identification of TWSG1as a second novel erythroid regulator of hepcidin expression in murine and human cells[J].Blood,2009,114:181-186.
[12]Shah YM,Matsubara T,Ito S,et al.Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency[J].Cell Metab,2009,9:152-164.
[13]Rishi G,Wallace DF,Subramaniam VN.Hepcidin:regulation of the master iron regulator[J].Biosci Rep,2015,35:e00192.
[14]Delaby C,Pilard N,Puy H,et al.Sequential regulation of ferroportin expression after erythrophagocytosis in murine macrophages:early mRNA induction by haem,followed by iron-dependent protein expression[J].Biochem J,2008,411:123-131.
[15]Italia K,Colah R,Ghosh K.Experimental animal model to study iron overload and iron chelation and review of other such models[J].Blood Cells Mol Dis,2015,55:194-199.
[16]Porter JB,de Witte T,Cappellini MD,et al.New insights into transfusion-related iron toxicity:Implications for the oncologist[J].Crit Rev Oncol Hematol,2016,99:261-271.
[17]Cabantchik ZI,Breuer W,Zanninelli G,et al.LPI-labile plasma iron in iron overload[J].Best Pract Res Clin Haematol,2005,18:277-287.
[18]Zuo Y,Xiang B,Yang J,et al.Oxidative modification of caspase-9facilitates its activation via disulfide-mediated interaction with Apaf-1[J].Cell Res,2009,19:449-457.
[19]Alessandrino EP,Della Porta MG,Bacigalupo A,et al.Prognostic impact of pre-transplantation transfusion history and secondary iron overload in patients with myelodysplastic syndrome undergoing allogeneic stem cell transplantation:a GITMO study[J].Haematologica,2010,95:476-484.
[20]Tachibana T,Tanaka M,Takasaki H,et al.Pretransplant serum ferritin is associated with bloodstream infections within 100days of allogeneic stem cell transplantation for myeloid malignancies[J].Int J Hematol,2011,93:368-374.
[21]Jacobi N,Herich L.Measurement of liver iron concentration by superconducting quantum interference device biomagnetic liver susceptometry validates serum ferritin as prognostic parameter for allogeneic stem cell transplantation[J].Eur J Haematol,2016,97:336-341.
[22]Anderson LJ.Assessment of iron overload with T2*magnetic resonance imaging[J].Prog Cardiovasc Dis,2011,54:287-294.
[23]Dohner H,Estey E,Grimwade D,et al.Diagnosis and management of AML in adults:2017ELN recommendations from an international expert panel[J].Blood,2017,129:424-447.
[24]Tachibana T,Tanaka M,Yamazaki E,et al.Multicenter validation of scoring system of pre-transplant serum ferritin and disease risk in patients with acute myeloid leukemia and myelodysplastic syndrome after allogeneic hematopoietic stem cell transplant[J].Leuk Lymphoma,2013,54:1318-1320.
[25]Finke J,Schmoor C,Bertz H,et al.Long-term followup of therapy-related myelodysplasia and AML patients treated with allogeneic hematopoietic cell transplantation[J].Bone Marrow Transplant,2016,51:771-777.
[26]Boehm A,Sperr WR,Kalhs P,et al.Long-term followup after allogeneic stem cell transplantation in patients with myelodysplastic syndromes or secondary acute myeloid leukemia:a single center experience[J].Wien Klin Wochenschr,2014,126:23-29.
[27]Atilla E,Toprak SK,Demirer T.Current review of iron overload and related complications in hematopoietic stem cell transplantation[J].Turk J Haematol,2017,34:1-9.
[28]Kim YR,Kim JS,Cheong JW,et al.Transfusion-associated iron overload as an adverse risk factor for transplantation outcome in patients undergoing reduced-intensity stem cell transplantation for myeloid malignancies[J].Acta Haematol,2008,120:182-189.
[29]Komrokji RS,Corrales-Yepez M,Kharfan-Dabaja MA,et al.Hypoalbuminemia is an independent prognostic factor for overall survival in myelodysplastic syndromes[J].Am J Hematol,2012,87:1006-1009.
[30]Jang JE,Kim SJ,Cheong JW,et al.Early CMV replication and subsequent chronic GVHD have a significant anti-leukemic effect after allogeneic HSCT in acute myeloid leukemia[J].Ann Hematol,2015,94:275-282.
[31]Lim ZY,Fiaccadori V,Gandhi S,et al.Impact of pretransplant serum ferritin on outcomes of patients with myelodysplastic syndromes or secondary acute myeloid leukaemia receiving reduced intensity conditioning allogeneic haematopoietic stem cell transplantation[J].Leuk Res,2010,34:723-727.
[32]Artz AS,Logan B,Zhu X,et al.The prognostic value of serum C-reactive protein,ferritin,and albumin prior to allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndromes[J].Haematologica,2016,101:1426-1433.
[33]Yan Z,Chen X,Wang H,et al.Effect of pre-transplantation serum ferritin on outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation:A meta-analysis[J].Medicine(Baltimore),2018,97:e10310.
[34]Pileggi C,Di Sanzo M,Mascaro V,et al.Role of serum ferritin level on overall survival in patients with myelodysplastic syndromes:Results of a meta-analysis of observational studies[J].PLoS One,2017,12:e0179016.