title: Identification of a novel fusion gene involving RUNX1 and the antisense strand of SV2B in a BCR-ABL1-positive acute leukemia.
abstract: RUNX1, a key regulator of hematopoiesis, is frequently mutated or implicated in chromosomal translocations in acute leukemia. About half of RUNX1 translocations remain uncharacterized at the molecular level. We describe here one such event, a t(15;21)(q26.1;q22) translocation identified in an adult patient diagnosed with a t(9;22)(q34;q11.2)-positive acute leukemia. This previously unreported rearrangement yields a fusion of RUNX1 with the antisense strand of the SV2B gene, a new translocation partner of RUNX1, resulting in the expression of out-of-frame mRNA chimeric transcripts and the production of putative truncated RUNX1 isoforms. The t(15;21) translocation also dissociates the P1 promoter of RUNX1 from its open reading frame, reducing RUNX1 expression levels in the patient's leukemic cells. Our data suggest that RUNX1 haploinsufficiency collaborates with the BCR-ABL1 oncogene in this leukemia. The description of this atypical gene fusion is an important addition to the characterization of the pathogenomic mechanisms leading to RUNX1 structural and functional alterations. Furthermore, our data strongly suggests that inadequate dosage of this gene plays an essential role in leukemogenesis.
authors.affiliation: Quebec Leukemia Cell Bank and Hematology-Oncology Division, Maisonneuve-Rosemont Hospital, 5415 L'Assomption Blvd., Montréal H1T 2M4, Canada; Department of Medicine, Université de Montréal, C.P. 6128, succursale Centre-ville, Montréal H3C 3J7, Canada.
authors.forename: Amélie
authors.initials: A
authors.lastname: Giguère
authors.forename: Josée
authors.initials: J
authors.lastname: Hébert
mesh_terms: D000328:Adult; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics*; D016373:DNA, Antisense / Q000235:genetics*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D007438:Introns; D008562:Membrane Glycoproteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D027361:Organic Anion Transporters / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011401:Promoter Regions, Genetic; D014178:Translocation, Genetic
chemical_list: C581634:BCR-ABL1 fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D016373:DNA, Antisense; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D015514:Oncogene Proteins, Fusion; D027361:Organic Anion Transporters; C479544:SLCO3A1 protein, human; C489616:SV2B protein, human; D016044:Fusion Proteins, bcr-abl