title: ABL1 fusion genes in hematological malignancies: a review.
abstract: Chromosomal rearrangements involving the ABL1 gene, leading to a BCR-ABL1 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 ABL1. 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 (BCR-ABL1, ETV6-ABL1, ZMIZ1-ABL1, EML1-ABL1, and NUP214-ABL1) have transforming activity, although NUP214-ABL1 requires amplification to be efficient. The NUP214-ABL1 gene is the second most prevalent fusion gene involving ABL1 in malignant hemopathies, with a frequency of 5% in T-cell ALL. Both fusion genes (SFPQ-ABL1 and RCSD1-ABL1) characterized by a break in intron 4 of ABL1 are associated with B-cell ALL, as the chimeric proteins lacked the SH2 domain of ABL1. Screening for ABL1 chimeric genes could be performed in patients with ALL, more particularly in those with T-cell ALL because ABL1 modulates T-cell development and plays a role in cytoskeletal remodeling processes in T cells.
authors: Université de Brest, Faculté de Médecine et des Sciences de la Santé, Brest Institut National de la Santé et de la Recherche Médicale (INSERM), Brest CHRU Brest, Hôpital Morvan, Service de Cytogénétique, Cytologie et Biologie de la Reproduction, Brest, France.
authors: Etienne
authors: E
authors: De Braekeleer
authors: Nathalie
authors: N
authors: Douet-Guilbert
authors: David
authors: D
authors: Rowe
authors: Nick
authors: N
authors: Bown
authors: Frédéric
authors: F
authors: Morel
authors: Christian
authors: C
authors: Berthou
authors: Claude
authors: C
authors: Férec
authors: Marc
authors: M
authors: De Braekeleer
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016313:Genes, abl; D019337:Hematologic Neoplasms / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D050596:Oncogene Fusion; D016374:Oncogene Proteins v-abl / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D000072670:PTB-Associated Splicing Factor; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D016374:Oncogene Proteins v-abl; D015514:Oncogene Proteins, Fusion; D000072670:PTB-Associated Splicing Factor; D011505:Protein-Tyrosine Kinases; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C501947:EML1-ABL1 fusion protein, human; C521114:NUP214-ABL1 fusion protein, human; C506059:RCSD1 protein, human; C426234:TEL-ABL fusion protein, human; D000097764:ETS Translocation Variant 6 Protein; C480599:ZMIZ1 protein, human