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Stem cell kinetics

C J Eaves1, A C Eaves

  • 1Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada.

Bailliere'S Clinical Haematology
|June 1, 1997
PubMed
Summary

Chronic myeloid leukaemia (CML) involves a hierarchical clone similar to normal blood cell development. The BCR-ABL gene product influences differentiation, cell cycle, and apoptosis, explaining CML

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Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Chronic myeloid leukaemia (CML) is a multi-lineage disease characterized by a hierarchical leukaemic clone.
  • In its chronic phase, CML resembles normal haematopoiesis, making primitive progenitor cells difficult to distinguish.

Purpose of the Study:

  • To investigate the characteristics of primitive progenitors in CML patients.
  • To elucidate the role of the BCR-ABL gene product in CML pathogenesis during the chronic phase.

Main Methods:

  • Utilizing in vitro colony-forming cell (CFC) assays.
  • Employing long-term culture-initiating cell (LTC-IC) assays.
  • Analyzing primitive progenitors in patient blood and marrow samples.

Main Results:

  • Identified subsets of BCR-ABL positive cells indistinguishable from normal counterparts.
  • Observed unique findings regarding the numbers, properties, genotype, distribution, and regulation of primitive progenitors.
  • Demonstrated competing effects of BCR-ABL on differentiation commitment, cell cycle control, and apoptosis.

Conclusions:

  • The indolent nature of CML's chronic phase is attributed to the complex effects of BCR-ABL.
  • BCR-ABL constrains stem cell amplification but enhances progeny expansion, particularly on the granulocyte pathway.
  • Unchecked expansion of granulocyte precursors leads to the characteristic leukaemic picture.

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