Expression of p210 and p190 BCR-ABL due to alternative splicing in chronicmyelogenous leukaemia

The hallmark of chronic myelogenous leukaemia (CML) is the presence of the Philadelphia chromosome and its resultant fusion message, BCR-ABL, and fusi on protein. p210. Patients with CML in blast crisis, or with Philadelphia p ositive acute lymphoblastic leukaemia (ALL), can have a smaller BCR-ABL fus ion transcript possessing only the first er;on of BCR fused to ABL. This sm aller transcript encodes a 190 kD protein which is more strongly transformi ng than the p210 protein derived from the larger CML-associated transcript. We performed RT-PCR on samples from CML patients in chronic phase to deter mine the frequency and mechanism of p190 and p210 co-expression and to see if this correlated with clinical indices. We examined the peripheral blood or marrow of 67 patients with CML and foun d that 35 of them expressed both transcripts whereas the remainder expresse d the p210-encoding transcript exclusively Additional PCR products of an in termediate size were also frequently detected and hare been isolated and se quenced. Data from two of these products indicate that they are the result of alternative splicing and include variable combinations of BCR exons. We believe that the expression of the p190-encoding transcript in the chronic phase of CR-IL is also due to alternative splicing. A comparison of patient s co-expressing the p190 and p210-encoding transcripts with those patients who expressed only the p210-encoding transcript detected significantly high er white blood cell (WBC) counts and blast cell counts at time of testing a s well as significantly higher white blood cell counts at diagnosis.