<i>ABL1</i> fusion genes in hematological malignancies: a review

<jats:title>Abstract</jats:title><jats:p>Chromosomal rearrangements involving the <jats:italic>ABL1</jats:italic> gene, leading to a <jats:italic>BCR‐ABL1</jats:italic> fusion gene, have been mainly associated with chronic myeloid leukemia and B‐cell acute lymphoblastic leukemia (ALL). At present, six other genes have been shown to fuse to <jats:italic>ABL1</jats:italic>. The kinase domain of ABL1 is retained in all chimeric proteins that are also composed of the N‐terminal part of the partner protein that often includes a coiled‐coil or a helix‐loop‐helix domain. These latter domains allow oligomerization of the protein that is required for tyrosine kinase activation, cytoskeletal localization, and neoplastic transformation. Fusion genes that have a break in intron 1 or 2 (<jats:italic>BCR‐ABL1</jats:italic>, <jats:italic>ETV6‐ABL1</jats:italic>, <jats:italic>ZMIZ1‐ABL1</jats:italic>, <jats:italic>EML1‐ABL1</jats:italic>, and <jats:italic>NUP214‐ABL1</jats:italic>) have transforming activity, although <jats:italic>NUP214‐ABL1</jats:italic> requires amplification to be efficient. The <jats:italic>NUP214‐ABL1</jats:italic> gene is the second most prevalent fusion gene involving <jats:italic>ABL1</jats:italic> in malignant hemopathies, with a frequency of 5% in T‐cell ALL. Both fusion genes (<jats:italic>SFPQ‐ABL1</jats:italic> and <jats:italic>RCSD1‐ABL1</jats:italic>) characterized by a break in intron 4 of <jats:italic>ABL1</jats:italic> are associated with B‐cell ALL, as the chimeric proteins lacked the SH2 domain of ABL1. Screening for <jats:italic>ABL1</jats:italic> chimeric genes could be performed in patients with ALL, more particularly in those with T‐cell ALL because <jats:italic>ABL1</jats:italic> modulates T‐cell development and plays a role in cytoskeletal remodeling processes in T cells.</jats:p>