FLT3-ITD突变的急性髓系白血病免疫表型及临床特征分析
|
摘要
目的讨论FLT3-ITD突变的急性髓系白血病(AML)的免疫表型及临床特征。方法回顾性分析2015年6月—2017年6月中国医科大学附属第四医院收治的FLT3-ITD+及FLT3-ITD-AML组患者的免疫表型、临床资料,并对两组患者化疗后临床结局及生存状况进行比较。结果 FLT3-ITD+AML组患者CD56、CD33、CD11b及CD7表达高于FLT3-ITD-AML组(P <0.05),而CD34、CD117表达低于FLT3-ITD-AML组(P <0.05)。与FLT3-ITD-AML组患者比较,FLT3-ITD+AML组患者外周血白细胞计数及骨髓原始细胞比例升高(P<0.05),而血红蛋白及血小板计数比较,差异无统计学意义(P>0.05);FLT-ITDAML组患者总反应率高于FLT3-ITD+AML组(P<0.05);FLT3-ITD-AML组患者无病生存率和总生存率高于FLT3-ITD+AML组(P<0.05)。FLT3-ITD+AML组患者完全缓解患者CD56、CD34、CD11b、CD7、CD33及CD117的表达水平低于未缓解患者(P<0.05)。结论 FLT3-ITD+AML患者白血病细胞抗原表达紊乱,外周血白细胞及骨髓原始细胞高,完全缓解率低,预后差,是AML预后不良因素。AML患者早期检测FLT3-ITD突变及免疫分型对于指导治疗、判断预后具有重要临床意义。
Objective To study immunophenotype and clinical characteristics of acute myeloid Leukemia(AML) with FLT3-ITD positive. Methods The immunophenotype and laboratory characteristics of FLT3-ITD+and FLT3-ITD-acute myeloid leukemia patients admitted to our hospital from June 2015 to June 2017 were retrospectively analyzed. The clinical outcomes and survival of the two groups after chemotherapy were compared. Results The expression of CD56, CD33, CD11 b, CD7 in FLT3-ITD+AML patients was much higher than that in FLT3-ITDAML patients, while the expressions of CD34 and CD117 were much lower(P < 0.05); the white blood cell count and bone marrow leukemia cells in FLT3-ITD+AML patients increased much more than those in FLT3-ITD-AML patients(P < 0.05), while there was no statistical difference in hemoglobin and platelet count(P > 0.05); the rate of treatment objective response(OR) in FLT3-ITD+AML patients was much higher than that in FLT3-ITD-AML patients(P < 0.05); Patient-free survival and overall survival in FLT3-ITD-AML patients were much higher than those in FLT3-ITD+AML patients(P < 0.05). The expressions of CD56, CD34, CD11 b, CD7, CD34 and CD117 in FLT3-ITD+patients with complete remission were significantly lower than those in patients without remission(P < 0.05). Conclusions The abnormal expression of leukemia cell antigen, high peripheral blood leukocytes and bone marrow primordial cells, low complete remission rate and poor prognosis in patients with FLT3-ITD+AML are the poor prognostic factors of AML. Early detection of FLT3-ITD mutation and immunotyping in AML patients has important clinical significance in guiding treatment and judging prognosis.
Objective To study immunophenotype and clinical characteristics of acute myeloid Leukemia(AML) with FLT3-ITD positive. Methods The immunophenotype and laboratory characteristics of FLT3-ITD+and FLT3-ITD-acute myeloid leukemia patients admitted to our hospital from June 2015 to June 2017 were retrospectively analyzed. The clinical outcomes and survival of the two groups after chemotherapy were compared. Results The expression of CD56, CD33, CD11 b, CD7 in FLT3-ITD+AML patients was much higher than that in FLT3-ITDAML patients, while the expressions of CD34 and CD117 were much lower(P < 0.05); the white blood cell count and bone marrow leukemia cells in FLT3-ITD+AML patients increased much more than those in FLT3-ITD-AML patients(P < 0.05), while there was no statistical difference in hemoglobin and platelet count(P > 0.05); the rate of treatment objective response(OR) in FLT3-ITD+AML patients was much higher than that in FLT3-ITD-AML patients(P < 0.05); Patient-free survival and overall survival in FLT3-ITD-AML patients were much higher than those in FLT3-ITD+AML patients(P < 0.05). The expressions of CD56, CD34, CD11 b, CD7, CD34 and CD117 in FLT3-ITD+patients with complete remission were significantly lower than those in patients without remission(P < 0.05). Conclusions The abnormal expression of leukemia cell antigen, high peripheral blood leukocytes and bone marrow primordial cells, low complete remission rate and poor prognosis in patients with FLT3-ITD+AML are the poor prognostic factors of AML. Early detection of FLT3-ITD mutation and immunotyping in AML patients has important clinical significance in guiding treatment and judging prognosis.
引文
[1]NOGAMI A,OSHIKAWA G,OKADA K,et al.FLT3-ITD confers resistance to the PI3K/Akt pathway inhibitors by protecting the mTOR/4EBP1/Mcl-1 pathway through STAT5 activation in acute myeloid leukemia[J].Oncotarget,2015,6(11):9189-9205.
[2]CHAUHAN P S,IHSAN R,SINGH L C,et al.Mutation of NPMl and FLT3 genes in acute myeloid leukemia and their association with clinical and immunophenotypic features[J].Dis Markers,2013,35(5):581.
[3]TAMAMYAN G,KADIA T,RAVANDI F,et al.Frontline treatment of acute myeloid leukemia in adults[J].Crit Rev Oncol Hematol,2017,110:20-34.
[4]中美联合上海市白血病协作组.468例急性白血病患者FLT3基因突变及其预后价值分析[J].中华血液学杂志,20l0,31(1):1.
[5]徐媛媛,高丽,丁一,等.急性髓系白血病中FLT3-ITD基因突变的检测及其临床意义[J].中国实验血液学杂,2012,20(6):1312.
[6]ALMAWALI A,GILLIS D,LEWIS I.Characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplication in the FLT3 gene[J].Oman Med J,2013,28(6):432.
[7]MESHINCHI S,APPELBAUM F R.Structural and functional alterations of FLT3 in acute myeloid leukemia[J].Clin Cancer Res,2009,15(13):4263.
[8]李玲,吕晓东,米瑞华,等.急性髓系白血病患者NPM1,FLT3-ITD和C-KIT基因突变检测及其预后分析[J].中国实验血液学杂志,2013,21,(3):601-606.
[9]LIU YAN,KE X Y,WANG J,et al.Clinical characteristics and prognosis of acute myeloid leukemiawith FLT3-ITD mutation[J].Journal of Experimental Hematology,2018,26(2):354-358.
[10]CHEN Y,LI X M,MA T,et al.Analysis of immunophenotype and clinical features in AML patients with FLT3-ITD positive[J].Journal of Military Surgeon in Southwest China,2016,18(4):308-310.
[11]M U N O Z L,AV E N T I A A,V I L L A M O R N,e t a l.Immunophenotypic findings in acute myeloid leukemia with FLT3 internal tandem duplication[J].Haematologica,2008,88(6):637.
[12]DANG H,JIANG A,KAMEL-REID S,et al.Prognostic value of immunophenotyping and gene mutations in elderly patients with acute myeloid leukemia with normal karyotype[J].Hum Pathol,2013,44(1):55-61.
[13]CHAUHAN P S,IHSAN R,SINGH L C,et al.Mutation of NPMl and FLT3 genes in acute myeloid leukemia and their association with clinical and immunophenotypic features[J].Dis Markers,2013,35(5):581.
[14]KERKENT W,CHAHWAN C,LENORMAND C,et al.Usefulness of urethral endoprosthesis in the management of urinary retention after brachytherapy for localized prostate cancer[J].Prog Urol,2014,24(3):164.
[15]葛繁梅,刘延香,任羽,等.急性髓系白血病128例免疫表型与预后的关系研究[J].陕西医学杂志,2014,43(4):454-456.
[16]CHEN M H,ATENAFU E,CRADDOCK K J,et a1.CDllb expression correlates with monosomal karyotype and predicts anextremely poor prognosis in cytogenetically unfavorable acute myeloid leukemia[J].Leuk Res,2013,37(2):122.
[17]刘延方,朱颖超,张秋堂,等.FLT3-ITD突变急性髓系白血病的临床及免疫表型特征分析[J].郑州大学学报,2015,50(3):441-443.
[2]CHAUHAN P S,IHSAN R,SINGH L C,et al.Mutation of NPMl and FLT3 genes in acute myeloid leukemia and their association with clinical and immunophenotypic features[J].Dis Markers,2013,35(5):581.
[3]TAMAMYAN G,KADIA T,RAVANDI F,et al.Frontline treatment of acute myeloid leukemia in adults[J].Crit Rev Oncol Hematol,2017,110:20-34.
[4]中美联合上海市白血病协作组.468例急性白血病患者FLT3基因突变及其预后价值分析[J].中华血液学杂志,20l0,31(1):1.
[5]徐媛媛,高丽,丁一,等.急性髓系白血病中FLT3-ITD基因突变的检测及其临床意义[J].中国实验血液学杂,2012,20(6):1312.
[6]ALMAWALI A,GILLIS D,LEWIS I.Characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplication in the FLT3 gene[J].Oman Med J,2013,28(6):432.
[7]MESHINCHI S,APPELBAUM F R.Structural and functional alterations of FLT3 in acute myeloid leukemia[J].Clin Cancer Res,2009,15(13):4263.
[8]李玲,吕晓东,米瑞华,等.急性髓系白血病患者NPM1,FLT3-ITD和C-KIT基因突变检测及其预后分析[J].中国实验血液学杂志,2013,21,(3):601-606.
[9]LIU YAN,KE X Y,WANG J,et al.Clinical characteristics and prognosis of acute myeloid leukemiawith FLT3-ITD mutation[J].Journal of Experimental Hematology,2018,26(2):354-358.
[10]CHEN Y,LI X M,MA T,et al.Analysis of immunophenotype and clinical features in AML patients with FLT3-ITD positive[J].Journal of Military Surgeon in Southwest China,2016,18(4):308-310.
[11]M U N O Z L,AV E N T I A A,V I L L A M O R N,e t a l.Immunophenotypic findings in acute myeloid leukemia with FLT3 internal tandem duplication[J].Haematologica,2008,88(6):637.
[12]DANG H,JIANG A,KAMEL-REID S,et al.Prognostic value of immunophenotyping and gene mutations in elderly patients with acute myeloid leukemia with normal karyotype[J].Hum Pathol,2013,44(1):55-61.
[13]CHAUHAN P S,IHSAN R,SINGH L C,et al.Mutation of NPMl and FLT3 genes in acute myeloid leukemia and their association with clinical and immunophenotypic features[J].Dis Markers,2013,35(5):581.
[14]KERKENT W,CHAHWAN C,LENORMAND C,et al.Usefulness of urethral endoprosthesis in the management of urinary retention after brachytherapy for localized prostate cancer[J].Prog Urol,2014,24(3):164.
[15]葛繁梅,刘延香,任羽,等.急性髓系白血病128例免疫表型与预后的关系研究[J].陕西医学杂志,2014,43(4):454-456.
[16]CHEN M H,ATENAFU E,CRADDOCK K J,et a1.CDllb expression correlates with monosomal karyotype and predicts anextremely poor prognosis in cytogenetically unfavorable acute myeloid leukemia[J].Leuk Res,2013,37(2):122.
[17]刘延方,朱颖超,张秋堂,等.FLT3-ITD突变急性髓系白血病的临床及免疫表型特征分析[J].郑州大学学报,2015,50(3):441-443.