期刊
LEUKEMIA
卷 19, 期 3, 页码 442-448出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.leu.2403650
关键词
BCR-ABL; leukemogenesis; NOD/SCID mice; gene transfer
In this study, we describe the successful use of a gene transfer approach to demonstrate the ability of forced BCR-ABL expression to deregulate the growth and differentiation of primitive naive human hematopoietic cells after their transplantation into immunodeficient mice. Human CD34(+) cord blood cells were exposed to an MSCV retrovirus containing a BCR-ABL-IRES- GFP (P210) cassette and then injected immediately into sublethally irradiated nonobese diabetic-severe combined immunodeficiency (NOD/SCID) or NOD/SCID-beta2microglobulin(-/-) mice. P210- and control-transduced (GFP(+)) human hematopoietic cells were produced in the bone marrow of the mice at similar levels until termination of the experiments 5 - 6 months later. However, the P210- transduced cells produced a markedly different spectrum of progeny, with an increased ratio of myeloid to B-lymphoid cells and a frequently prolonged increase in erythroid and megakaryocytic cells. After 5 months, several of the mice transplanted with P210- transduced cells developed an increased WBC count and/or splenomegaly due to an expansion of the human GFP(+) population. These findings demonstrate that forced expression of BCR-ABL in primitive transplantable human hematopoietic cells is sufficient to cause a rapid and persistent deregulation of their growth and differentiation in vivo with occasional evidence after several months of progression to an early stage of disease.
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