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- W2027824715 abstract "Chronic myelomonocytic leukemia (CMML) is a unique myeloproliferative disease characterized by marrow dysplasia and an increase in monocytes. The median survival of patients with CMML is short, in part, because CMML is frequently resistant to therapy. A better understanding of the basic biology of CMML progenitors is needed in order to reduce regimen related toxicity and provide more effective CMML targeted therapies. To this end, a mouse transgenic model of CMML was created in which human bcl-2 overexpression was targeted to the myeloid lineage by the myeloid promoter hMRP8. Transgenic hMRP8-bcl2 mice developed a myeloproliferative disorder characterized by a monocytosis in all hematopoietic tissues and splenomegaly. Myeloid progenitor analysis of hMRP8-bcl-2 bone marrow revealed a marked expansion of human bcl-2 expressing granulocyte-macrophageprogenitors compared with control mice. In order to see if thiscorrelated with human CMML, we used FACS analysisand recently identified phenotypic markers to identify phenotypicand functional differences between normal and CMML bonemarrow hematopoietic stem cells and myeloid progenitors. CMML marrow was typified by a reduction in CD34+CD38−CD90+Lin− hematopoietic stem cells and an expansion of CD34+CD38−CD90−Flk2+Lin− cells relative to normal bone marrow. In addition, there was a two-fold expansion in common myeloid progenitors (CMPs) and a corresponding decrease in megakaryocyte-erythroid progenitors (MEPs) suggesting that there was a skew in differentiation toward the myeloid lineage. In contrast to normal bone marrow derived CMPs, CMML CMPs gave rise to myeloid but not erythroid colonies. Moreover, real time quantitative RT-PCR analysis of highly purified FACS-sorted CMML CMPs demonstrated increased expression of two key regulators of myelomonocytic differentiation, PU.1 and c-jun, compared with normal bone marrow. A more detailed understanding of the basic biology of CMML progenitors and the genes that work in concert to expand them may aid in identifying novel molecular targets for CMML." @default.
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- W2027824715 date "2005-02-01" @default.
- W2027824715 modified "2023-10-18" @default.
- W2027824715 title "Prognostic progenitor profiling in chronic myelomonocytic leukemia" @default.
- W2027824715 doi "https://doi.org/10.1016/j.bbmt.2004.12.176" @default.
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