Hematopoietic cell fate and the initiation of leukemic properties in primitive primary human cells are influenced by Ras activity and farnesyltransferase inhibition.

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 Biol

authors

Dorrell C,Takenaka K,Minden MD,Hawley RG,Dick JE

doi

10.1128/MCB.24.16.6993-7002.2004

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

6993-7002

issue

16

eissn

0270-7306

issn

1098-5549

pii

24/16/6993

journal_volume

24

pub_type

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