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

144 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 - Jan 1 1998
Externally publishedYes

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Acute Myeloid Leukemia
Apoptosis
Bone Marrow
Myelopoiesis
Myeloid Progenitor Cells
Myeloid Cells
Ligation
Neoplasms
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Mice defective in two apoptosis pathways in the myeloid lineage develop acute myeloblastic leukemia. / Traver, David; Akashi, Koichi; Weissman, Irving L.; Lagasse, Eric.

In: Immunity, Vol. 9, No. 1, 01.01.1998, p. 47-57.

Research output: Contribution to journalArticle

Traver, David ; Akashi, Koichi ; Weissman, Irving L. ; Lagasse, Eric. / Mice defective in two apoptosis pathways in the myeloid lineage develop acute myeloblastic leukemia. In: Immunity. 1998 ; Vol. 9, No. 1. pp. 47-57.
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