Identification of human chronic myelogenous leukemia progenitor cells with hemangioblastic characteristics.
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-1-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.
Fang
Baijun
B
Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
Zheng
Chunmei
C
Liao
Lianming
L
Han
Qin
Q
Sun
Zhao
Z
Jiang
Xueying
X
Zhao
Robert C H
RC
D000293:Adolescent; D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000209:etiology* / Q000473:pathology*; D008099:Liver / Q000166:cytology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D018952:Antigens, CD34; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D016044:Fusion Proteins, bcr-abl