title: Inhibition of apoptosis by BCR-ABL in chronic myeloid leukemia.
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.
authors.affiliation: Johns Hopkins Oncology Center, Johns Hopkins Medical Institutions, Baltimore, MD 21287-8967.
authors.forename: A
authors.initials: A
authors.lastname: Bedi
authors.forename: B A
authors.initials: BA
authors.lastname: Zehnbauer
authors.forename: J P
authors.initials: JP
authors.lastname: Barber
authors.forename: S J
authors.initials: SJ
authors.lastname: Sharkis
authors.forename: R J
authors.initials: RJ
authors.lastname: Jones
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D016044:Fusion Proteins, bcr-abl / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008224:Lymphoma, Follicular / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data
chemical_list: D007377:Interleukin-3; D016044:Fusion Proteins, bcr-abl