ABLI Rearrangements in T-Cell Acute Lymphoblastic Leukemia

作者：Hagemeijer Anne^*; Graux Carlos

来源：Genes, Chromosomes and Cancer, 2010, 49(4): 299-308.

DOI：10.1002/gcc.20743

T-cell acute lymphoblastic leukemia (TALL) is the result of multiple oncogenic insults of thymocytes. Recently, new ABLI fusion genes have been identified that provide proliferation and survival advantage to lymphoblasts. These are the NUP2 14-ABLI fusion gene, on amplified episomes, the unique case of EMLI-ABLI fusion due to a cryptic t(9;14)(q34;q32) and the seldom reported BCR-ABLI and ETV6-ABLI chimeric genes. The most frequent and strictly associated with TALL is the NUP214-ABLI 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 ABLI fusion is a late event associated with other genetic alterations like NOTCHI activating mutation, deletion of CDKN2A locus, and ectopic expression of TLXI or TLX3. The mechanism of activation of the NUP214-ABLI protein is unique and requires localization at the nucleopore complex and interaction with other nuclear pore proteins for crossphosphorylation and constitutive kinase activity. The ABLI fusion proteins are sensitive to tyrosine kinase inhibitors, which can be included in future treatment strategy.

• 出版日期2010-4