Mice defective in two afoptosis pathways in the myeloid lineage develop acute myeloblastic leukemia

P. Traver, K. Akashi, I. L. Weissman, E. Lagasse

Research output: Contribution to journalArticlepeer-review


Fas-deficient (FaslPr/lpr/) mice constitutively expressing Bcl-2 in myeloid cells by the hMRPS promoter develop a fatal disease analogous to human acute myeloblastic leukemia (AML-M2). Hematopoietic cells from leukemic FaslPr/lpr hMRP8bcl-2 animals form clonogenic blast colonies in vitro and can transfer disease to wild-type recipient animals. These data demonstrate that loss of function Fas mutations synergistically collaborate with gain of function Bcl-2 mutations in the development of AML. In vitro ligation of Fas on Fas+/+ hMRP8bcl-2 bone marrow cells depletes approximately 50% of myeloid progenitor activity, demonstrating that Bcl-2 can only partially block Fas-mediated death signals in myelomonocytic progenitors. In addition, FaslPr/lPr marrow contains greatly increased numbers of myeloid colony-forming cells as compared to Fas+/+ controls. Taken together, these data suggest that Fas has a novel role in the regulation of myelopoiesis and that Fas may act as a tumor suppressor to control leukemogenic transformation in myeloid progenitor cells.

Original languageEnglish
Number of pages1
JournalExperimental Hematology
Issue number8
Publication statusPublished - Dec 1 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research


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