Abl Gene - Clinical Significance

Clinical Significance

Mutations in the ABL1 gene are associated with chronic myelogenous leukemia (CML). In CML, the gene is activated by being translocated within the BCR (breakpoint cluster region) gene on chromosome 22. This new fusion gene, BCR-ABL, encodes an unregulated, cytoplasm-targeted tyrosine kinase that allows the cells to proliferate without being regulated by cytokines. This, in turn, allows the cell to become cancerous.

This gene is a partner in a fusion gene with the BCR gene in the Philadelphia chromosome, a characteristic abnormality in chronic myelogenous leukemia (CML) and rarely in some other leukemia forms. The BCR-ABL transcript encodes a tyrosine kinase, which activates mediators of the cell cycle regulation system, leading to a clonal myeloproliferative disorder. The BCR-ABL protein can be inhibited by various small molecules. One such inhibitor is imatinib mesylate, which occupies the tyrosine kinase domain and inhibits BCR-ABL's influence on the cell cycle. Second generation BCR-ABL tyrosine-kinase inhibitors are also under development to inhibit BCR-ABL mutants resistant to imatinib.