*3.1.1 The t(9;22)(q34;q11.2)(BCR-ABL1)*

The BCR/ABL1 or Philadelphia (Ph) chromosome is a t(9;22) product that fuses the chromosome 9 Abelson kinase gene (ABL1) with the chromosome 22 breakpoint cluster region (BCR) that expresses the fusion protein BCR-ABL1: a constitutively active tyrosine kinase. The breakpoint occurs between exons 1 and 2 (e1 and e2) of the BCR gene in the minor breakpoint cluster region, m-BCR, in the majority of Ph positive ALL patients, and between exons 1 and 2 of the ABL gene in the majority of Ph positive ALL patients (e1a2). This results in the development of a 7-kb mRNA and the expression of the p190 protein [13]. This transcribes an 8.5 kb mRNA that codes for a chimeric p210 protein [14]. The Philadelphia chromosome is the most important cytogenetic abnormality. It is seen in 3% of pediatric patients, and almost 25% of adults, and rises with age, reflecting about half of the cases of patients older than 60 years of age, and although historically associated with poor prognosis, results have been markedly improved with the use of tyrosine kinase inhibitors (TKIs) [15].
