Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia

Atul Bedi, Barbara A. Zehnbauer, James P. Barber, Saul J. Sharkis, Richard J Jones

Research output: Contribution to journalArticle

Abstract

BCR-ABL expression is presumed to effect clonal expansion in chronic myeloid leukemia (CML) by deregulation of cell proliferation. However, most studies have found that relative rates of cell proliferation are not increased in CML. Moreover, we found that CML progenitors display a normal proliferative response to growth factors and do not manifest greater proliferative potential than normal progenitors. Growth of malignancies depends on an imbalance between the rate of cell production and the rate of cell death. We found that BCR-ABL expression inappropriately prolongs the growth factor-independent survival of CML myeloid progenitors and granulocytes by inhibiting apoptosis, a genetically programmed process of active cell death; inhibition of BCR-ABL expression by antisense oligonucleotides reversed the suppression of apoptosis as well as the enhancement of survival. The decreased rate of programmed cell death appears to be the primary mechanism by which BCR-ABL effects expansion of the leukemic clone in CML.

Original languageEnglish (US)
Pages (from-to)2038-2044
Number of pages7
JournalBlood
Volume83
Issue number8
StatePublished - Apr 15 1994

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Cell death
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cell proliferation
Apoptosis
Intercellular Signaling Peptides and Proteins
Cell Death
Deregulation
Antisense Oligonucleotides
Cell Proliferation
Granulocyte Precursor Cells
Clone Cells
Growth
Neoplasms

ASJC Scopus subject areas

  • Hematology

Cite this

Bedi, A., Zehnbauer, B. A., Barber, J. P., Sharkis, S. J., & Jones, R. J. (1994). Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia. Blood, 83(8), 2038-2044.

Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia. / Bedi, Atul; Zehnbauer, Barbara A.; Barber, James P.; Sharkis, Saul J.; Jones, Richard J.

In: Blood, Vol. 83, No. 8, 15.04.1994, p. 2038-2044.

Research output: Contribution to journalArticle

Bedi, A, Zehnbauer, BA, Barber, JP, Sharkis, SJ & Jones, RJ 1994, 'Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia', Blood, vol. 83, no. 8, pp. 2038-2044.
Bedi A, Zehnbauer BA, Barber JP, Sharkis SJ, Jones RJ. Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia. Blood. 1994 Apr 15;83(8):2038-2044.
Bedi, Atul ; Zehnbauer, Barbara A. ; Barber, James P. ; Sharkis, Saul J. ; Jones, Richard J. / Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia. In: Blood. 1994 ; Vol. 83, No. 8. pp. 2038-2044.
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