Progenitor tumours from Emu-bcl-2-myc transgenic mice have lymphomyeloid differentiation potential and reveal developmental differences in cell survival

EMBO J. 1996 Aug 1;15(15):3823-34.

Abstract

Mice expressing both a bcl-2 and a myc transgene within the B lymphoid cell compartment invariably develop novel immature haemopoietic tumours. The likely cell of origin of these tumours was identified by a common pattern of cell surface marker expression on a subset of cells comprising approximately 1% of normal mouse bone marrow. The bcl-2-myc tumour cells could be induced to differentiate into either B lymphocytes or macrophages in culture with certain cytokines and feeder cells. Analysis of their progression into the B lymphoid lineage revealed that Igk locus transcription can precede Igh as well as Igk rearrangement. Surprisingly, the undifferentiated tumour cells died rapidly in culture, even in the presence of multiple cytokines, but they proliferated on monolayers of stromal cells derived from haemopoietic tissues. Thus, even with Bcl-2 levels that protect more differentiated cells, these immature bi-potential progenitor cells require a stromal-induced signal for survival. These results provide insight into the process of lineage commitment and suggest new levels of control of cell survival during early steps in haemopoietic development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • Base Sequence
  • Blotting, Northern
  • Cell Differentiation*
  • Cell Survival
  • DNA Primers
  • Gene Expression Regulation, Leukemic
  • Genes, myc*
  • Hematopoietic Stem Cells / cytology*
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / pathology
  • Macrophages / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Phenotype
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-2
  • Stromal Cells / cytology
  • Transcription, Genetic
  • Transgenes

Substances

  • DNA Primers
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2