BCR/ABL genes and leukemic phenotype: from molecular mechanisms to clinical correlations

The Philadelphia chromosome (Ph), a minute chromosome that derives from the balanced translocation between chromosomes 9 and 22, was first described in 1960 and was for a long time the only genetic lesion consistently assocd. with human cancer. This chromosomal translocation results in the fusion between the 5' part of BCR gene, normally located on chromosome 22, and the 3' part of the ABL gene on chromosome 9 giving origin to a BCR/ABL fusion gene which is transcribed and then translated into a hybrid protein. Three main variants of the BCR/ABL gene have been described, that, depending on the length of the sequence of the BCR gene included, encode for the p190BCR/ABL, P210BCR/ABL, and P230BCR/ABL proteins. These three main variants are assocd. with distinct clin. types of human leukemias. Herein we review the data on the correlations between the type of BCR/ABL gene and the corresponding leukemic clin. features. Lastly, drawing on exptl. data, we provide insight into the different transforming power of the three hybrid BCR/ABL proteins.