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背景:Flt3基因是近年来发现的早期造血生长因子受体基因。Flt3与其配体结合后能通过信号传导途径对造血干/祖细胞的增殖和分化起调节作用。Flt3近膜区的内部串联重复(FLT3/ITD)与多种白血病的发生,发展密切相关,且为预后不良的独立指标。目的:探讨Flt-3基因内部串联重复(ITD)突变与急性白血病发生的关系及其预后判断的临床意义。设计:重复测量。单位:沈阳医学院生物化学及分子生物教研室。对象:147例样本均来自于1999-01/2004-12沈阳医学院附属医院住院及门诊收治的白血病患者,均经形态学及骨髓活检确诊。其中男95例,女52例;年龄5~23岁。参照FAB分型标准诊断:急性髓性白血病62例患者分别为AML(M1,M2)33例,AMMOL(M4)3例,AMOL(M5)18例,AMKL(M7)8例,急性淋巴细胞白血病43例,幼年型慢性粒细胞白血病13例,骨髓增生异常综合征29例。纳入对象均对检测项目知情同意。方法:采用聚合酶链反应联合序列检测147例白血病患者中的Flt-3/ITD。主要观察指标:观察伴有Flt-3/ITD急性髓性白血病患者的临床表现及预后,检测各类急性白血病中Flt-3的表达水平及Flt-3/ITD阳性率,发生的区间和长度。结果:①Flt-3/ITD:急性髓性白血病患者62例中有5例除Flt-3表达产物之外,伴有异常扩增产物,其中急性髓性白血病(M1,M2)3例、AM-MOL1例、AMOL1例。测序及Blast比对分析显示,伴有异常产物的患者在外显子11区均有ITD,各例ITD的复制区域不同,长短不等(33~72bp)。43例急性淋巴细胞白血病、29例骨髓增生异常综合征和13例幼年型慢性粒细胞白血病患者中均未检测到Flt-3/ITD。②预后:5例Flt-3/ITD阳性患者确诊后均在短期内死亡,平均生存期10.8个月。结论:①Flt-3/ITD仅发现于急性髓性白血病患者,其存在可能与急性髓性白血病发生及进展有关。②Flt-3/ITD是急性髓性白血病患者预后判断的重要标志。
Background: The Flt3 gene is an early hematopoietic growth factor receptor gene found in recent years. Flt3 binds to its ligand and regulates the proliferation and differentiation of hematopoietic stem / progenitor cells through signaling pathways. Flt3 proximal membrane region of the internal tandem repeat (FLT3 / ITD) and a variety of leukemia is closely related to the development, and an independent prognosis of poor prognosis. Objective: To investigate the relationship between Flt-3 gene tandem duplication (ITD) mutation and the occurrence of acute leukemia and the clinical significance of its prognosis. Design: repeat measurement. Unit: Department of Biochemistry and Molecular Biology, Shenyang Medical College. PARTICIPANTS: All the 147 samples were from leukemia patients hospitalized and outpatient in Shenyang Medical College Hospital from January 1999 to December 2004, all confirmed by morphology and bone marrow biopsy. There were 95 males and 52 females, aged 5 to 23 years old. According to FAB classification criteria, 62 cases of acute myeloid leukemia were AML (M1, M2) 33 cases, AMMOL (M4) 3 cases, AMOL (M5) 18 cases, AMKL (M7) 8 cases, acute lymphoblastic leukemia 43 cases, juvenile chronic myeloid leukemia in 13 cases, myelodysplastic syndrome in 29 cases. Subjects involved in the informed consent of the test items. Methods: Flt-3 / ITD was detected in 147 patients with leukemia by polymerase chain reaction (PCR). MAIN OUTCOME MEASURES: The clinical manifestations and prognosis of patients with Flt-3 / ITD acute myeloid leukemia were observed. The expression of Flt-3 and the positive rate of Flt-3 / ITD and the interval and length of Flt-3 / ITD were detected in all kinds of acute leukemia. Results: ①Flt-3 / ITD: Among the 62 cases of acute myeloid leukemia, 5 cases had abnormal amplification products in addition to the Flt-3 expression product, including 3 cases of acute myeloid leukemia (M1 and M2), 3 cases of AM- 1 case of MOL, 1 case of AMOL. Sequencing and Blast analysis showed that patients with abnormal products had ITD in exon 11 and cases of ITD varied in length from 33 to 72 bp. No Flt-3 / ITD was detected in 43 cases of acute lymphoblastic leukemia, 29 cases of myelodysplastic syndrome and 13 cases of juvenile myeloid leukemia. ② Prognosis: 5 cases of Flt-3 / ITD positive patients died within a short period after diagnosis, with an average survival of 10.8 months. Conclusion: ①Flt-3 / ITD is only found in patients with acute myeloid leukemia, its existence may be related to the occurrence and progression of acute myeloid leukemia. ②Flt-3 / ITD is an important marker of prognosis in patients with acute myeloid leukemia.