Pre-B acute lymphoblastic leukemia with b3a2 (p210) and e1a2 (p190) BCR-ABL fusion transcripts relapsing as chronic myelogenous leukemia with a less differentiated b3a2 (p210) clone

The Philadelphia chromosome translocation t(9;22)(q34;q11) may give rise to different BCR/ABL fusion mRNAs due to different genomic breakpoints and al ternative splicing. The e1a2, b2a2 or b3a2 and c3a2 fusion mRNAs encode dis tinct fusion proteins (p190, p210 and p230, respectively), which are associ ated with different forms of leukemogenesis in humans and animal models. Ou r patient presented with acute pre-B cell lymphoblastic leukemia (ALL) with normal cytogenetics. After 3 years of standard ALL therapy, he relapsed wi th t(9;22)-positive chronic myelogenous leukemia (CML). Retrospective molec ular analyses of the pre-treatment pre-B cell ALL sample showed the b3a2 (p 210) and e1a2 (p190) BCR/ABL fusion transcripts. Only the b3a2 (p210) trans cript was detected at relapse. Southern and immunoglobulin heavy chain (IgH ) analyses of the presentation and relapse samples revealed an identical BC R rearrangement in both samples. However, only the ALL sample harbored an I gH gene rearrangement. These findings show a clonal relationship between th e more differentiated pre-B cell and less differentiated CML clones and tha t the p210 and p190 fusion mRNAs were alternatively spliced from a single g enomic breakpoint. Our patient's unusual molecular findings provide circums tantial evidence that the p190 protein may promote a more differentiated ph enotype in a comparatively less differentiated p210-transformed precursor c ell.