Chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL) are both commonly associated with a specific chromosome translocation, t(9;22)(q34;q11). The derivative chromosome 22 is called the Philadelphia chromosome (Ph) and harbors the critical fusion gene.
At least 95% of CML cases have an identifiable t(9;22), while approximately 6% of pediatric ALL patients and up to 25% of adult ALLs have this translocation. Some of these exchanges of chromosomal material are cryptic or present in a low percentage of the cells and cannot be detected by standard cytogenetic analysis, warranting the use of a molecular approach. The t(9;22) results in the fusion of a portion of the breakpoint cluster region gene (BCR) of chromosome 22 with the ABL proto-oncogene, encoding a tyrosine kinase, from chromosome 9.
Transcription of the fusion gene results in a hybrid mRNA composed of portions of both BCR and ABL gene transcripts. This fusion gene is under control of the BCR gene promoter and transcription of the fusion mRNA occurs at a greater rate than that of the normal ABL gene. Translation of the fusion transcript results in either a 210 kD (P210) or 190 kD (P190) protein, which has increased tyrosine kinase activity.
