P53 GENE-MUTATIONS WITH CHROMOSOME-17 ABNORMALITIES IN CHRONIC MYELOGENOUS LEUKEMIA BLAST CRISIS PATIENTS PERSIST IN LONG-TERM CELL-LINES BUT MAY BE ACQUIRED IN ACUTE MYELOID-LEUKEMIA CELLS IN-VITRO

Altered p53 tumor suppressor genes have been described in various human malignancies, including in chronic myelogenous leukemias (CML) and acute myelogenous leukemias (AML), os well as their derivative cell lines. It has been proposed that this gene mutation may be less frequent in myeloid leukemia patients than in myeloid leukemia cell lines and that the latter acquire these mutations during growth in vitro. We investigated this possibility by studying p53 gene alterations in marched samples of fresh leukemic cells and their respective derivative cell lines obtained from two CML blast crisis and one AML patient. No gross structural abnormalities were detected in the p53 gene in any of the samples analyzed. Discrete mutations in the gene in the two CML blast crisis samples and in all three derivative cell lines were, however, detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analyses and DNA sequencing. Cytogenetic analyses revealed either numerical or structural, as well as numerical, abnormalities of chromosome 17 in their karyotypes. Cells from the two CML blast crisis patients had two different mutations which were maintained as the sole mutations in the cell lines. The mutation detected in the AML cell line was, however, not detectable in the parental fresh leukemic cells. Our findings demonstrate that p53 mutations and chromosome 17 abnormalities occurring in CML blast crisis patients persist in long-term cell lines but that mutations not detectable in AML patients may indeed be acquired in cell lines established from them in vitro.