Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia
Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia
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DOI：
10.1038/nm1253
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发表时间：
2005-06-01
期刊：
影响因子：
82.9
通讯作者：
Jacobsen, SEW
中科院分区：
文献类型：
--
作者：
Castor, A;Nilsson, L;Jacobsen, SEW
在大多数癌症中，原发突变和恶性转化的细胞靶标仍然难以捉摸。在这里，我们表明临床和遗传上不同的急性淋巴细胞白血病（ALL）亚型在造血发育的不同阶段起源和转化。原代 ETV6-RUNX1（也称为 TEL-AML1）融合和随后的白血病转化针对定型 B 细胞祖细胞。主要断点 BCR-ABL1 融合（编码 P210 BCR-ABL1）起源于造血干细胞（HSC），而次要 BCR-ABL1 融合（编码 P190 BCR-ABL1）具有 B 细胞祖细胞起源，表明 P190 和 P210 BCR-ABL1 ALL 代表了很大程度上不同的肿瘤生物学和临床实体。与 ETV6-RUNX1 ALL 一样，P190 和 P210 BCR-ABL1 ALL 中转化的白血病起始干细胞都具有定型 B 祖细胞表型。在所有患者中，正常和白血病再生干细胞都可以成功地进行前瞻性分离，值得注意的是，ETV6-RUNX1 和 P190 BCR-ABL1 ALL 中正常 HSC 区室的大小被发现不受白血病干细胞群扩张的影响。
The cellular targets of primary mutations and malignant transformation remain elusive in most cancers. Here, we show that clinically and genetically different subtypes of acute lymphoblastic leukemia ( ALL) originate and transform at distinct stages of hematopoietic development. Primary ETV6-RUNX1 ( also known as TEL-AML1) fusions and subsequent leukemic transformations were targeted to committed B-cell progenitors. Major breakpoint BCR-ABL1 fusions ( encoding P210 BCR-ABL1) originated in hematopoietic stem cells (HSCs), whereas minor BCR-ABL1 fusions ( encoding P190 BCR-ABL1) had a B-cell progenitor origin, suggesting that P190 and P210 BCR-ABL1 ALLs represent largely distinct tumor biological and clinical entities. The transformed leukemia-initiating stem cells in both P190 and P210 BCR-ABL1 ALLs had, as in ETV6-RUNX1 ALLs, a committed B progenitor phenotype. In all patients, normal and leukemic repopulating stem cells could successfully be separated prospectively, and notably, the size of the normal HSC compartment in ETV6-RUNX1 and P190 BCR-ABL1 ALLs was found to be unaffected by the expansive leukemic stem cell population.