Mice Defective in Two Apoptosis Pathways in the Myeloid Lineage Develop Acute Myeloblastic Leukemia
Copyright policy )Mice Defective in Two Apoptosis Pathways in the Myeloid Lineage Develop Acute Myeloblastic Leukemia
Fas-deficient (Fas(lpr/lpr)) 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(lpr/lpr)hMRP8bcl-2 animals form clonogenic blast colonies in vitro and can transfer disease to wild-type mice. In vitro ligation of Fas on Fas+/+ hMRP8bcl-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(lpr/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.
- Stanford University United States
Male, Mice, Inbred MRL lpr, Immunology, Apoptosis, Bone Marrow Cells, Mice, Transgenic, Lymphocyte Activation, Mice, Immunology and Allergy, Animals, Humans, Calgranulin A, Calcium-Binding Proteins, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoietic Stem Cells, Antigens, Differentiation, Causality, Leukemia, Myeloid, Acute, Infectious Diseases, Proto-Oncogene Proteins c-bcl-2, Female, Interleukin-3, Neoplasm Transplantation
Male, Mice, Inbred MRL lpr, Immunology, Apoptosis, Bone Marrow Cells, Mice, Transgenic, Lymphocyte Activation, Mice, Immunology and Allergy, Animals, Humans, Calgranulin A, Calcium-Binding Proteins, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoietic Stem Cells, Antigens, Differentiation, Causality, Leukemia, Myeloid, Acute, Infectious Diseases, Proto-Oncogene Proteins c-bcl-2, Female, Interleukin-3, Neoplasm Transplantation
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