不同类型成人白血病中Fms样酪氨酸激酶（FLT）3及FLT3内部串联重复：147例患者分析

Fms-like tyrosine kinase (FLT) 3 and FLT3 internal tandem duplication in different types of adult leukemia: analysis of 147 patients.

作者信息

Peng Hong-Ling, Zhang Guang-Sen, Gong Fan-Jie, Shen Jian-Kai, Zhang Yang, Xu Yun-Xiao, Zheng Wen-Li, Dai Chong-Wen, Pei Min-Fei, Yang Jun-Jie

机构信息

Division of Hematology/Institute of Molecular Hematology, Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

出版信息

Croat Med J. 2008 Oct;49(5):650-69. doi: 10.3325/cmj.2008.5.650.

DOI:10.3325/cmj.2008.5.650

PMID:18925699

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2582358/

Abstract

AIM

To assess the expression level of fms-like tyrosine kinase 3 (FLT3), the incidence of FLT3/internal tandem duplications (ITD) mutation, and prognostic value of FLT3 changes in different types of adult leukemia.

METHODS

Bone marrow mononuclear cells were isolated from 147 adult patients with leukemia. Reverse transcriptase polymerase chain reaction (PCR) was used to screen FLT3/ITD mutation and quantitative PCR was performed to evaluate the expression of the FLT3 transcript. Flow cytometry was used for detection of FLT3 receptor protein expression on bone marrow mononuclear cells. Pearson correlation analysis was performed to estimate the significance of FLT3.

RESULTS

FLT3 expression was higher in acute myeloid leukemia and B-acute lymphoid leukemia than in T-acute lymphoid leukemia (P=0.006, P=0.001) and chronic myelogenous leukemia (P<0.001). In chronic myelogenous leukemia, FLT3 expression in blast transformation phase was higher than in acceleration phase (P=0.023). Surface expression of FLT3 protein was correlated with high percentage of bone marrow blasts and with FLT3 mRNA expression (r=0.366, P<0.001) in acute leukemia. FLT3/ITDs in the juxtamembrane domain were found in 25% of patients with acute myeloid leukemia and 7% of patients with acute lymphoid leukemia. FLT3/ITD positive sequences had 36, 42, and 57 nucleotides. FLT3/ITD mutation was associated with a higher white blood cell count, higher marrow blast percentage, and elevated serum lactate dehydrogenase (P=0.045, P=0.014, P<0.001, respectively) and not associated with a higher FLT3 mRNA and FLT3 protein expression, and lower complete remission (P=0.091, P=0.060, P=0.270, respectively).

CONCLUSION

FLT3 expression levels differed in different types of adult leukemia. Overexpression of FLT3 and presence of a positive FLT3/ITD mutation in acute leukemia were associated with unfavorable clinical characteristics and poor prognosis.

摘要

目的

评估成人不同类型白血病中fms样酪氨酸激酶3（FLT3）的表达水平、FLT3内部串联重复（ITD）突变的发生率以及FLT3变化的预后价值。

方法

从147例成年白血病患者中分离出骨髓单个核细胞。采用逆转录聚合酶链反应（PCR）筛选FLT3/ITD突变，并进行定量PCR以评估FLT3转录本的表达。采用流式细胞术检测骨髓单个核细胞上FLT3受体蛋白的表达。进行Pearson相关性分析以评估FLT3的意义。

结果

急性髓系白血病和B系急性淋巴细胞白血病中的FLT3表达高于T系急性淋巴细胞白血病（P = 0.006，P = 0.001）和慢性髓性白血病（P < 0.001）。在慢性髓性白血病中，急变期的FLT3表达高于加速期（P = 0.023）。在急性白血病中，FLT3蛋白的表面表达与骨髓原始细胞高比例以及FLT3 mRNA表达相关（r = 0.366，P < 0.001）。在25%的急性髓系白血病患者和7%的急性淋巴细胞白血病患者中发现了近膜结构域中的FLT3/ITD。FLT3/ITD阳性序列有36、42和57个核苷酸。FLT3/ITD突变与白细胞计数升高、骨髓原始细胞百分比升高以及血清乳酸脱氢酶升高相关（分别为P = 0.045，P = 0.014，P < 0.001），与FLT3 mRNA和FLT3蛋白表达升高以及完全缓解率降低无关（分别为P = 0.091，P = 0.060，P = 0.270）。