EXPRESSION OF DIFFERENT CONFORMATIONS OF P53 IN THE BLAST CELLS OF ACUTE MYELOBLASTIC-LEUKEMIA IS RELATED TO IN-VITRO GROWTH-CHARACTERISTICS

Expression of the wild-type p53 gene has an important role in cell dif ferentiation, maturation and apoptosis. Mutation of the p53 gene is as sociated with tumour development and mutant p53 can promote cell proli feration. 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 h ave analysed the expression of p53 by flow cytometry in blast cells fr om 34 patients with acute myeloblastic leukaemia in relationship to th e proliferation characteristics of these cells in a clonogenic assay. Blasts from three out of 34 patients did not express p53 using the ant ibodies: PAb421, PAb1801, PAb240 and PAb1620. The remaining 31 samples expressed p53 detected by PAb240 which recognises mutant p53 and is p redicted to recognise wild-type p53 in the promoter conformation. Blas ts from 19 out of 31 cells which expressed PAb240 co-expressed PAb1620 , expression of PAb1620 was associated with non-autonomous growth in v itro. In contrast, the majority of blasts with the p53 phenotype of PA b240+/PAb1620- or which lacked p53 expression exhibited autonomous gro wth characteristics in vitro. Furthermore expression of PAb1620 in bla sts with autonomous growth cells could be detected following growth in hibition using monoclonal antibodies against autocrine growth factors. Our data demonstrate that in AML cells, p53 conformation is related t o the growth characteristics of the cells and is regulated by either e xogenous or autocrine haematopoietic growth factors.