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- W1994010908 abstract "Expression of c-Myb is required for normal hematopoiesis and for proliferation of myeloid leukemia blasts and a subset of T-cell leukemia, but its role in B-cell leukemogenesis is unknown. We tested the role of c-Myb in p190BCR/ABL-dependent B-cell leukemia in mice transplanted with p190BCR/ABL-transduced marrow cells with a c-Myb allele (Mybf/d) and in double transgenic p190BCR/ABL/Mybw/d mice. In both models, loss of a c-Myb allele caused a less aggressive B-cell leukemia. In p190BCR/ABL-expressing human B-cell leukemia lines, knockdown of c-Myb expression suppressed proliferation and colony formation. Compared with c-Mybw/f cells, expression of Bmi1, a regulator of stem cell proliferation and maintenance, was decreased in pre-B cells from Mybw/d p190BCR/ABL transgenic mice. Ectopic expression of a mutant c-Myb or Bmi1 enhanced the proliferation and colony formation of Mybw/d p190BCR/ABL B-cells; by contrast, Bmi1 downregulation inhibited colony formation of p190BCR/ABL-expressing murine B cells and human B-cell leukemia lines. Moreover, c-Myb interacted with a segment of the human Bmi1 promoter and enhanced its activity. In blasts from 19 Ph1 adult acute lymphoblastic leukemia patients, levels of c-Myb and Bmi1 showed a positive correlation. Together, these findings support the existence of a c-Myb–Bmi1 transcription-regulatory pathway required for p190BCR/ABL leukemogenesis." @default.
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- W1994010908 date "2011-09-30" @default.
- W1994010908 modified "2023-10-14" @default.
- W1994010908 title "c-Myb and its target Bmi1 are required for p190BCR/ABL leukemogenesis in mouse and human cells" @default.
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- W1994010908 doi "https://doi.org/10.1038/leu.2011.264" @default.
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