Clonal variation of the immunogenotype in relapsed ETV6/RUNX1-positive acute lymphoblastic leukemia indicates subclone formation during early stages of leukemia development

Clonal variation of the immunogenotype in relapsed ETV6/RUNX1-positive acute lymphoblastic leukemia indicates subclone formation during early stages of leukemia development
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DOI:
10.1002/gcc.10305
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发表时间:
2004-02-01
影响因子:
3.7
通讯作者:
Panzer-Grümayer, ER
Panzer-Grümayer, ER
中科院分区:
医学2区
文献类型:
--
作者:
Peham, M;Konrad, M;Panzer-Grümayer, ER

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最近的数据表明,晚期复发是从祖先ETV 6/RUNXI阳性(也称为TEL/AMLI阳性)克隆演变而来的,这些克隆是由与初始白血病不同的继发性变化(ETV 6缺失)引起的,因此也可能在其克隆型免疫球蛋白/T细胞受体(IG/TCR)基因重排中发生偏离。本研究的目的是比较12例早期或晚期复发儿童的未重排ETV 6等位基因的免疫基因型和荧光原位杂交(FISH)模式的匹配诊断/复发样本。我们确定了其中6例的IG/TCR存在不同程度的差异。在六名儿童中还观察到未重排的ETV 6等位基因的克隆变化或进化,但在三名儿童中保持不变。然而,这两个参数并不一致,也没有免疫基因型模式与首次缓解的持续时间。因此,我们提出免疫基因型多样化的潜力主要取决于ETV 6/RUNXI基因融合发生的细胞的IG/TCR基因构型的阶段。(C)2003 Wiley-Liss,Inc.
Recent data suggest that late relapses evolve from an ancestral ETV6/RUNXI-positive (also designated TEL/AMLI-positive) clone resulting from secondary changes (ETV6 deletion) that differ from those of the initial leukemia and, as a consequence, may also deviate in their clonotypic immunoglobulin/T-cell receptor (IG/TCR) gene rearrangements. The aim of our study was to compare the immunogenotype and fluorescence in situ hybridization (FISH) patterns of the unrearranged ETV6 allele of matched diagnosis/relapse samples from 12 children with an early or late relapse. We identified varying degrees of differences in the IG/TCR in six of them. A clonal change or evolution of the unrearranged ETV6 allele was also observed in six children but remained unchanged in three. However, these two parameters were not in concordance, nor did the immunogenotype pattern correlate with the duration of the first remission. We therefore propose that the potential of the immunogenotype to diversify depends primarily on the stage of IG/TCR gene configuration of the cell in which the ETV6/RUNXI gene fusion takes place. (C) 2003 Wiley-Liss, Inc.