Mutants of a multipotent hematopoietic cell line blocked in GM-CSF-induced differentiation are leukemogenic in vivo

Exp Hematol. 1994 Aug;22(9):933-40.

Abstract

FDCP-Mix cells infected with a retroviral vector expressing the GM-CSF gene (GMV-FDCP-Mix) self-renew in the presence of interleukin-3 (IL-3), are multipotent, and undergo differentiation into granulocytes and macrophages coupled with clonal extinction after removal of IL-3. Mutants of GMV-FDCP-Mix were isolated that escape clonal extinction after differentiation induction by the autocrine secreted GM-CSF. Some of these mutant clones have a blast cell morphology and are blocked in differentiation, whereas others exhibit all stages of granulocyte and macrophage differentiation without clonal extinction. In contrast to the parental GMV-FDCP-Mix cells, all the mutants tested were leukemogenic when injected into syngeneic mice. Depending on the in vitro differentiation capacity of the transplanted mutant cell lines, the animals developed undifferentiated blast cell leukemias or CML-like syndromes. Thus, these mutant cell lines can be used to define the cooperating steps in autocrine myeloid leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Line
  • Cell Transformation, Neoplastic / pathology*
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / genetics
  • Gene Expression Regulation
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
  • Granulocytes / cytology
  • Granulocytes / drug effects
  • Granulocytes / physiology
  • Hematopoiesis / physiology
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / physiology
  • Interleukin-3 / pharmacology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / etiology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / physiology
  • Mice
  • Mutation*

Substances

  • DNA, Neoplasm
  • Interleukin-3
  • Granulocyte-Macrophage Colony-Stimulating Factor