Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia
Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia
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DOI：
10.1182/blood.v97.1.89
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发表时间：
2001-01-01
期刊：
影响因子：
20.3
通讯作者：
Radich, JP
中科院分区：
文献类型：
--
作者：
Meshinchi, S;Woods, WG;Radich, JP
Flt 3基因编码一种调节造血干细胞增殖和分化的酪氨酸激酶受体。在急性髓细胞白血病（AML）中已报道了FIt 3基因的内部串联重复（Flt 3/ITD），并且可能与不良预后相关。我们分析了91例接受儿童癌症组（CCG）-2891治疗的儿童AML患者的诊断性骨髓标本中Flt 3/ITD的存在，并将其存在与临床结果相关联。91份样本中有15份（16.5%）为Flt 3/ITD阳性。Flt 3/ITD阳性患者的诊断白色计数中位数为73800，而Flt 3/ITD阴性患者的诊断白细胞计数中位数为28400（P = 0.05）。异常聚合酶链反应产物的核苷酸测序表明，所有重复涉及Flt 3基因的外显子11，也保留了阅读框架。谱系限制性分析显示，Flt 3/ITD不存在于淋巴细胞中，表明缺乏干细胞参与这种突变。Flt 3/ITD阳性患者均无不利的细胞遗传学标志物，也无特定FAB类别的优势。Flt 3/ITD阳性患者的缓解诱导率为40%，而Flt 3/ITD阴性患者为74%（P = 0.005）。Kaplan-Meier估计的Flt 3/ITD患者和非Flt 3/ITD患者的8年无事件生存率分别为7%和44%（P = 0.002）。多变量分析表明，Flt 3/ITD的存在是儿童AML预后不良（P = 0.009）的单一最重要的独立预后因素。(C)2001年，美国血液学会。
The Flt3 gene encodes a tyrosine kinase receptor that regulates proliferation and differentiation of hematopoietic stem cells. An internal tandem duplication of the FIt3 gene (Flt3/ITD) has been reported in acute myelogenous leukemia (AML) and may be associated with poor prognosis. We analyzed diagnostic bone marrow specimens from 91 pediatric patients with AML treated on Children's Cancer Group (CCG)-2891 for the presence of the Flt3/ITD and correlated its presence with clinical outcome. Fifteen of 91 samples(16.5%) were positive for the Flt3/ITD. Flt3/ITD-positive patients had a median diagnostic white count of 73 800 compared with 28 400 for the Flt3/ITD-negative patients (P = .05), The size of the duplication ranged from 21 to 174 base pairs (bp). Nucleotide sequencing of the abnormal polymerase chain reaction products demonstrated that all duplications involved exon 11 of the Flt3 gene and also preserved the reading frame. Lineage restriction analysis revealed that Flt3/ITD was not present in the lymphocytes, suggesting a lack of stem cell involvement for this mutation. None of the Flt3/ITD-positive patients had unfavorable cytogenetic markers, and there was no predominance of a particular FAB class. The remission induction rate was 40% in Flt3/ITD-positive patients compared with 74% in Flt3/ITD-negative ones(P = .005), The Kaplan-Meier estimates of event-free survival at 8 years for patients with and without Flt3/ITD were 7% and 44%, respectively (P = .002). Multivariate analysis demonstrated that presence of the Flt3/ITD was the single most significant, independent prognostic factor for poor outcome (P = .009) in pediatric AML. (C) 2001 by The American Society of Hematology.