ABL1

About ABL1

ABL1 on chromosome 9q34.12 encodes a non receptor tyrosine kinase involved in cell differentiation, division, adhesion, and the response to stress. In chronic myeloid leukemia, a reciprocal translocation between chromosomes 9 and 22 fuses ABL1 to the BCR gene, creating the shortened Philadelphia chromosome, first described in 1960 by Peter Nowell and David Hungerford in Philadelphia. The resulting BCR ABL1 fusion protein is a constantly active tyrosine kinase that drives the leukemia. Imatinib, a tyrosine kinase inhibitor approved in 2001, transformed chronic myeloid leukemia from a frequently fatal disease into a chronic condition for most patients and became a landmark of targeted therapy. Later inhibitors were developed to overcome resistance mutations in the kinase domain. The fusion is also found in a subset of acute lymphoblastic leukemia.