ABL1 rearrangements in T-cell acute lymphoblastic leukemia.
T-cell acute lymphoblastic leukemia (T-ALL) is the result of multiple oncogenic insults of thymocytes. Recently, new ABL1 fusion genes have been identified that provide proliferation and survival advantage to lymphoblasts. These are the NUP214-ABL1 fusion gene, on amplified episomes, the unique case of EML1-ABL1 fusion due to a cryptic t(9;14)(q34;q32) and the seldom reported BCR-ABL1 and ETV6-ABL1 chimeric genes. The most frequent and strictly associated with T-ALL is the NUP214-ABL1 fusion identified in 6% of cases, in both children and adults. Patients present with classical T-ALL features. Cytogenetically, the fusion is cryptic but seen by FISH on amplified episomes or more rarely as a small hsr. The ABL1 fusion is a late event associated with other genetic alterations like NOTCH1 activating mutation, deletion of CDKN2A locus, and ectopic expression of TLX1 or TLX3. The mechanism of activation of the NUP214-ABL1 protein is unique and requires localization at the nucleopore complex and interaction with other nuclear pore proteins for crossphosphorylation and constitutive kinase activity. The ABL1 fusion proteins are sensitive to tyrosine kinase inhibitors, which can be included in future treatment strategy.
Hagemeijer
Anne
A
Department of Human Genetics, University of Leuven, Leuven, Belgium. Anne.Hagemeijer@med.kuleuven.be
Graux
Carlos
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics*
D015514:Oncogene Proteins, Fusion; D016315:Proto-Oncogene Proteins c-abl