Abstract:
:The Ras pathway transduces divergent signals determining normal cell fate and is frequently activated in hematopoietic malignancies, but the manner in which activation contributes to human leukemia is poorly understood. We report that a high level of activated H-Ras signaling in transduced primary human hematopoietic progenitors reduced their proliferation and enhanced monocyte/macrophage differentiation. However, the exposure of these cells to a farnesyltransferase inhibitor and establishment of a moderate level of Ras activity showed increased proliferation, an elevated frequency of primitive blast-like cells, and progenitors with enhanced self-renewal capacity. These results suggest that the amplitude of Ras pathway signaling is a determinant of myeloid cell fate and that moderate Ras activation in primitive hematopoietic cells can be an early event in leukemogenesis.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Dorrell C,Takenaka K,Minden MD,Hawley RG,Dick JEdoi
10.1128/MCB.24.16.6993-7002.2004subject
Has Abstractpub_date
2004-08-01 00:00:00pages
6993-7002issue
16eissn
0270-7306issn
1098-5549pii
24/16/6993journal_volume
24pub_type
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