Lymphocytic progenitor cell origin and clonal evolution of human B-lineage acute lymphoblastic leukemia
Lymphocytic progenitor cell origin and clonal evolution of human B-lineage acute lymphoblastic leukemia
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DOI：
10.1182/blood.v88.2.609.bloodjournal882609
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发表时间：
1996-07-15
期刊：
影响因子：
20.3
通讯作者：
Sklar, J
中科院分区：
文献类型：
--
作者：
Davi, F;Gocke, C;Sklar, J
目前，来自超过 25% 的 B 系急性淋巴细胞白血病 (ALL) 的骨髓标本在 Southern 印迹分析中显示出两次以上的免疫球蛋白重链 (IgH) 基因克隆重排。核苷酸序列分析显示这些基因之间主要存在不同的 V(H)DJ(H) 连接，导致此类病例经常被描述为寡克隆白血病。在本研究中，我们分析了四名患者的IgH基因，这些患者的白血病细胞在发病和复发之间含有不同模式的IgH基因重排，IgH基因的核苷酸序列分析表明三种机制可以解释这些差异：从头V(H)DJ(H)重排、V-H到DJ(H)重组和V-H替换。在所有情况下，在治疗过程中出现了两种以上完全不同的V(H)DJ(H)重排。该疾病的演变，与这些肿瘤由明显不相关的克隆组成的结论正式一致。然而，一些抗原受体基因重排的保留，以及两个病例中染色体标记的持续存在，表明这些白血病具有单克隆起源。这些发现支持这样的假设：一些 ALL 是由处于 IgH 基因重排开始之前的淋巴细胞发育阶段的淋巴祖细胞引起的。这些白血病淋巴细胞祖细胞产生能够在体内成熟的恶性子细胞，其涉及完成多种不同的IgH重排以及通过V-H到DJ(H)重组或通过V-H替换来修改先前存在的重排。 (C) 1996 年，美国血液学会。
At presentation, bone marrow specimens from over 25% of B-lineage acute lymphoblastic leukemias (ALL) display more than two clonal rearrangements of immunoglobulin heavy chain (IgH) genes in Southern blot analyses. Nucleotide sequence analysis has shown predominantly different V(H)DJ(H) junctions among these genes, leading to the frequent description of such cases as oligoclonal leukemias. In the present study, we have analyzed the IgH genes from four patients whose leukemic cells contained different patterns of IgH gene rearrangements between presentation and relapse, Nucleotide sequence analysis of the IgH genes showed that three mechanisms could account for these differences: de novo V(H)DJ(H) rearrangement, V-H to DJ(H) recombination, and V-H replacement, In all cases, more than two totally different V(H)DJ(H) rearrangements appeared during evolution of the disease, formally consistent with the conclusion that these tumors were composed of apparently unrelated clones. However, the retention of some of the antigen receptor gene rearrangements, as well as the persistence of a chromosomal marker in two cases, indicated that these leukemias had a monoclonal origin. These findings support the hypothesis that some ALLs arise from a lymphoid progenitor cell at a stage of lymphocyte development before the onset of IgH gene rearrangement. These leukemic lymphocyte progenitors generate malignant daughter cells capable of an in vivo maturation that involves the completion of multiple different IgH rearrangements as well as the modification of preexisting rearrangements by V-H to DJ(H) recombination or by a V-H replacement. (C) 1996 by The American Society of Hematology.