Retroviral transduction of Philadelphia-positive chronic myeloid leukemia cells with a human mutant p53 cDNA and its effect on in vitro proliferation.
Alterations in the tumor suppressor gene p53 are associated with the pathogenesis of blastic transformation of chronic myeloid leukemia (CML), but their exact role, particularly their relationship with the chimeric protein p210BCR/ABL, is poorly defined. Point mutations in p53 have been found in some cases of blast crisis and CML blastic cell lines, but it is not clear whether complete inactivation of p53 tumor suppressor function, with or without the production of a mutant protein, can by itself trigger the process of blastic transformation. By using retroviral gene transfer, we showed that the introduction of a mutant human p53 cDNA into hematopoietic progenitor cells from patients with CML in chronic phase, which already contain p210BCR/ABL, could promote their proliferation in vitro, and occasionally even lead to the growth of factor-independent colonies. We conclude that a mutant p53 may act in synergy with p210BCR/ABL and promote the survival and proliferation of CML hematopoietic stem and progenitor cells in vitro.
Bi
S
S
Department of Haematology, Royal Postgraduate Medical School, London, UK.
Barton
C M
CM
Lemoine
N R
NR
Cross
N C
NC
Goldman
J M
JM
D002455:Cell Division; D002478:Cells, Cultured; D002678:Chimera; D004273:DNA, Neoplasm / Q000235:genetics*; D004357:Drug Synergism; D016044:Fusion Proteins, bcr-abl / Q000494:pharmacology; D018014:Gene Transfer Techniques; D006133:Growth Substances / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology*; D008213:Lymphocyte Activation; D009154:Mutation / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics*; D014161:Transduction, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology*
D004273:DNA, Neoplasm; D006133:Growth Substances; D016159:Tumor Suppressor Protein p53; D016044:Fusion Proteins, bcr-abl