Functional alterations of Lin-CD34+CD38+ cells in chronic myelomonocytic leukemia and on progression to acute leukemia.
The functional behavior of hematopoietic stem cell (HSC) and progenitors in chronic myelomonocytic leukemia (CMML) and on disease progression is little known. We performed cell proliferation, apoptosis, hematopoietic colony forming/replating and differentiation potential studies in the purified subpopulations of Lin(-)CD34(+)CD38(-) and Lin(-)CD34(+)CD38(+) cells from 16 CMML with 6 cases after acute myeloid leukemia transformation (AML-t). We observed an expansion of the hematopoietic progenitor pool (Lin(-)CD34(+) cells) in AML-t comprising mainly Lin(-)CD34(+)CD38(+) cells. The Lin(-)CD34(+)CD38(+) cells in AML-t displayed high proliferative activity, resistance to apoptosis, enhanced myeloid colony formation/replating ability and a complete dendritic cell (DC) differentiation block. Our findings suggest Lin(-)CD34(+)CD38(+) cells instead of Lin(-)CD34(+)CD38(-) cells could be the target(s) of secondary genetic lesions underpinning progression from CMML to AML, which have implications for the further study of the biology of leukemic transformation and the design of new strategies for the effective treatment of CMML.
Sun
Qian
Q
SH Ho Foundation Research Laboratories, Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong SAR, China.
So
Chi-Chiu
CC
Yip
Sze-Fai
SF
Wan
Thomas S K
TS
Ma
Shiu-Kwan
SK
Chan
L C
LC
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D003114:Colony-Forming Units Assay; D003713:Dendritic Cells / Q000378:metabolism; D018450:Disease Progression; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006412:Hematopoietic Stem Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D015477:Leukemia, Myelomonocytic, Chronic / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018952:Antigens, CD34; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1