Expression of different conformations of p53 in the blast cells of acute myeloblastic leukaemia is related to in vitro growth characteristics.
Expression of the wild-type p53 gene has an important role in cell differentiation, maturation and apoptosis. Mutation of the p53 gene is associated with tumour development and mutant p53 can promote cell proliferation. Recently wild-type p53 has been demonstrated to exist in two conformational variants: one acting as a suppressor (PAb240-/PAb1620+) and one as a promoter (PAb240+/PAb1620-) of cell proliferation. We have analysed the expression of p53 by flow cytometry in blast cells from 34 patients with acute myeloblastic leukaemia in relationship to the proliferation characteristics of these cells in a clonogenic assay. Blasts from three out of 34 patients did not express p53 using the antibodies: PAb421, PAb1801, PAb240 and PAb1620. The remaining 31 samples expressed p53 detected by PAb240 which recognises mutant p53 and is predicted to recognise wild-type p53 in the promoter conformation. Blasts from 19 out of 31 cells which expressed PAb240 co-expressed PAb1620, expression of PAb1620 was associated with non-autonomous growth in vitro. In contrast, the majority of blasts with the p53 phenotype of PAb240+/PAb1620- or which lacked p53 expression exhibited autonomous growth characteristics in vitro. Furthermore expression of PAb1620 in blasts with autonomous growth cells could be detected following growth inhibition using monoclonal antibodies against autocrine growth factors. Our data demonstrate that in AML cells, p53 conformation is related to the growth characteristics of the cells and is regulated by either exogenous or autocrine haematopoietic growth factors.
Zhu
Y M
YM
Department of Haematology, Nottingham City Hospital, UK.
Bradbury
D
D
Russell
N
N
D000818:Animals; D002455:Cell Division; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D011487:Protein Conformation; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000737:chemistry
D016159:Tumor Suppressor Protein p53; D016178:Granulocyte-Macrophage Colony-Stimulating Factor