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

David Traver, Koichi Akashi, Irving L. Weissman, Eric Lagasse

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Fas-deficient (Fas(lprllpr)) mice constitutively expressing Bcl-2 in myeloid cells by the hMRP8 promoter often develop a fatal disease analogous to human acute myeloblastic leukemia (AML-M2). Hematopoietic cells from leukemic Fas(lprllpr)hMRP8bcl-2 animals form clonogenic blast colonies in vitro and can transfer disease to wild-type mice. In vitro ligation of Fas on Fas(+/+) hMRPSbcl-2 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, Fas(lprllpr) 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
Pages (from-to)47-57
Number of pages11
JournalImmunity
Volume9
Issue number1
DOIs
Publication statusPublished - Jul 1998
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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