Identification of human chronic myelogenous leukemia progenitor cells with hemangioblastic characteristics

被引:72
作者
Fang, BJ
Zheng, CM
Liao, LM
Han, Q
Sun, Z
Jiang, XY
Zhao, RCH
机构
[1] Chinese Acad Med Sci, Inst Hematol, Inst Basic Med Sci, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China
[2] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin 300020, Peoples R China
[3] Peking Union Med Coll, Tianjin 300020, Peoples R China
[4] Peking Union Med Coll, Beijing, Peoples R China
[5] Chinese Acad Med Sci, Inst Basic Med Sci, Beijing 100037, Peoples R China
[6] Chinese Acad Med Sci, Sch Basic Med, Beijing 100037, Peoples R China
[7] Chinese Acad Med Sci, Ctr Excellence Tissue Engn, Beijing 100037, Peoples R China
关键词
D O I
10.1182/blood-2004-07-2514
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Overwhelming evidence from leukemia research has shown that the clonal population of neoplastic cells exhibits marked heterogeneity with respect to proliferation and differentiation. There are rare stem cells within the leukemic population that possess extensive proliferation and self-renewal capacity not found in the majority of the leukemic cells. These leukemic stem cells are necessary and sufficient to maintain the leukemia. Interestingly, the BCR/ABL fusion gene, which is present in chronic myelogenous leukemia (CML), was also detected in the endothelial cells of patients with CML, suggesting that CML might originate from hemangioblastic progenitor cells that can give rise to both blood cells and endothelial cells. Here we isolated fetal liver kinase-l-positive (Flk1(+)) cells carrying the BCR/ABL fusion gene from the bone marrow of 17 Philadelphia chromosome-positive (Ph+) patients with CML and found that these cells could differentiate into malignant blood cells and phenotypically defined endothelial cells at the single-cell level. These findings provide direct evidence for the first time that rearrangement of the BCR/ABL gene might happen at or even before the level of hemangioblastic progenitor cells, thus resulting in detection of the BCR/ABL fusion gene in both blood and endothelial cells. (c) 2005 by The American Society of Hematology.
引用
收藏
页码:2733 / 2740
页数:8
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