FURTHER EVIDENCE FOR THE LACK OF CORRELATION BETWEEN THE BREAKPOINT SITE WITHIN M-BCR AND CML PROGNOSIS AND FOR THE OCCASIONAL INVOLVEMENT OF P53 IN TRANSFORMATION

The actual significance of the type of BCR-ABL rearrangement in chroni c myeloid leukemia (CML) prognosis remains controversial. Also, the mo lecular events that lead to CML progression ore largely unknown. We an alyzed the M-BCR breakpoint position in 64 CML patients by Southern bl ot and correlated the molecular findings with the cytogenetic, hematol ogic, and clinical data. No statistically significant differences were found with respect to the clinical and hemotologic data presented at diagnosis or in the median duration of chronic phase (CP) and survival between the groups of patients with 5' and 3' breakpoints. We also st udied by PCR-SSCP and direct sequencing the p53 gene in patients with specimens available in both chronic phase and blast crisis. We identif ied p53 mutations in 17% of the blast crisis samples analyzed, whereas no abnormalities were found in CP. This finding suggests that only in a minor fraction of cases are lesions in the p53 gene involved in tra nsformation. Given the present findings, along with previous reports, we believe that a novel mechanism to explain the heterogeneity of CML should be postulated and actively pursued, as should the identificatio n of secondary molecular events more consistently involved in progress ion.