Growth factor-mediated terminal differentiation of chronic myeloid leukemia.
Expression of the BCR-ABL chimeric gene in chronic myeloid leukemia results in the inhibition of apoptosis, a genetically programmed process of autonomous cell death. BCR-ABL and other genetic factors that suppress apoptosis confer cross-resistance to cytotoxic agents with diverse mechanisms of action. Eradication of the chronic myeloid leukemia clone requires strategies that circumvent this inherent resistance to cytotoxic therapy. We have determined that BCR-ABL expression augments the sensitivity of hematopoietic cells to growth factor-mediated signals of differentiation; hematopoietic growth factors induce the selective terminal differentiation of chronic myeloid leukemia progenitors at concentrations that allow optimal growth of normal progenitors. Hematopoietic growth factors may be an effective strategy for the elimination of cytotoxic therapy-resistant leukemic cells by inducing their terminal differentiation while allowing concomitant expansion of coexistent normal hematopoietic progenitors.
Bedi
A
A
Johns Hopkins Oncology Center, Baltimore, Maryland 21287-8967.
Griffin
C A
CA
Barber
J P
JP
Vala
M S
MS
Hawkins
A L
AL
Sharkis
S J
SJ
Zehnbauer
B A
BA
Jones
R J
RJ
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics*; D016313:Genes, abl / Q000235:genetics; D006098:Granulocytes / Q000473:pathology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011519:Proto-Oncogenes / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D007377:Interleukin-3; D016376:Oligonucleotides, Antisense