The BCR-ABL oncogene causes chronic myeloid leukemia (CML) and B-cell acute lymphoblastic leukemia (B-ALL) in human, and CML-like disease and lymphoid leukemia in mice. Recent studies show that cell adhesion molecule P-selectin is a potent negative regulator of human hematopoietic progenitors. Our previous work shows that lack of P-selectin accelerates the development of BCR-ABL-induced CML in mice (

Shawn et al,
Blood
,
104
[7]:
2163
-2171,
2004
, PMID: 15213099). We have observed that BCR-ABL-expressing Lin-c-Kit+ Sca-1+ bone marrow (BM) cells function as leukemic stem cells (LSCs). We tested whether LSCs play a role in the acceleration of CML development. We found that the percentage of LSCs in BM of P-selectin−/− CML mice was significantly higher than those in wild type C57BL/6 (B6) CML mice; other BM populations such as CMP, GMP, and MEP had no significant differences between the two groups of CML mice, suggesting that LSCs are responsible for the acceleration of CML disease when P-selectin is deficient. We also analyzed BM of B6 and P-selectin−/− mice and the BM of B6 and P-selectin−/− mice transplanted with BM transfected with empty vector virus. We found that there was no significant difference in the percentage of the stem cell population between the two groups of mice. This suggests that the higher percentage of LSCs in P-selectin−/− CML mice is caused by BCR-ABL but not by transplantation procedure associated with the P-selectin deficiency. Taken together, our results demonstrate that in CML mice, increased LSC population in P-selectin-deficient CML mice is associated with the acceleration of CML development.

Topics:
burkitt's lymphoma, leukemic hematopoietic stem cell, mice, selectins, p-selectin, bcr-abl tyrosine kinase, leukemia, b-cell, acute, cell adhesion molecules, cyclic gmp, leukemia, myelocytic, chronic

Disclosure: No relevant conflicts of interest to declare.

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2006, The American Society of Hematology
2006
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