CONSISTENT AMOUNTS OF ACUTE LEUKEMIA-ASSOCIATED P190BCR ABL TRANSCRIPTS ARE EXPRESSED BY CHRONIC MYELOGENOUS LEUKEMIA PATIENTS AT DIAGNOSIS/

In chronic myelogenous leukemia (CML), the Philadelphia (Ph) chromosom e translocation results in the formation of BCR/ABL genes, normally tr anscribed in two types of hybrid transcripts with a b2a2 or b3a2 BCR/A BL junction, which give origin to 210-kD fusion proteins (P210). A thi rd type of BCR/ABL (with e1a2 type of junction) has been identified in approximately 50% of the Ph-positive acute lymphoblastic leukemia (Ph +ALL) cases and results in the production of a BCR/ABL protein of 190 kD (P190). The presence of this transcript has been associated almost exclusively with the presence of an acute leukemia phenotype. By contr ast, here we describe that in addition to transcripts with the b2a2 an d b3a2 types of junction corresponding to the P210 proteins, virtually all CMLs at diagnosis bear also BCR/ABL transcripts showing the e1a2 type of junction, which correspond to the acute leukemia-associated P1 90 protein, With a quantitative polymerase chain reaction assay we fou nd that the amount of the e1a2 mRNA present in CMLs in chronic phase, although in absolute amount much lower than that present in Ph+ALLs, r epresents in most cases approximately 20% to 30% of the total BCR/ABL transcripts. Moreover, using a novel and very sensitive Western blot t echnique, we detected relevant amounts of P190 protein in addition to P210 from peripheral cells of two of the patients. (C) 1996 by The Ame rican Society of Hematology.