Novel RUNX1-PRDM16 fusion transcripts in a patient with acute myeloid leukemia showing t(1;21)(p36;q22)

• Published in: Genes chromosomes & cancer 2005-11, Vol.44 (3), p.265-270
• Main Authors: Sakai, Ikuya, Tamura, Tatsushiro, Narumi, Hirosi, Uchida, Naoyuki, Yakushijin, Yoshihiro, Hato, Takaaki, Fujita, Shigeru, Yasukawa, Masaki
• Format: Article
• Language: English
• Subjects: Aged; Alternative Splicing; Bone Marrow Cells - pathology; Chromosome Banding; Chromosomes, Human, Pair 1 - genetics; Chromosomes, Human, Pair 21 - genetics; Core Binding Factor Alpha 2 Subunit - genetics; DNA-Binding Proteins - genetics; Humans; Leukemia, Myelomonocytic, Acute - genetics; Male; Oncogene Proteins, Fusion - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Spectral Karyotyping; Transcription Factors - genetics; Translocation, Genetic
• ISSN: 1045-2257; 1098-2264
• DOI: 10.1002/gcc.20241

The t(1;21)(p36;q22) is a recurrent chromosome abnormality associated with therapy‐related acute myeloid leukemia (AML). Although involvement of RUNX1 has been detected by fluorescence in situ hybridization analysis, the partner gene has not been reported previously. We identified a novel RUNX1 partner gene, MDS1/EVI1‐like‐gene 1 (PRDM16), in an AML patient with t(1;21). Alternative splicing of the fusion gene generates five different fusion transcripts. In two of them, the PRDM16 reading frame is maintained in the fusion with RUNX1, suggesting that the RUNX1–PRDM16 gene fusion results in the production of a protein that is highly homologous to the RUNX1–MDS1/EVI1 chimeric protein. It is suggested that PRDM16 and MDS1/EVI1 share a common molecular mechanism for the leukemogenesis of RUNX1‐associated leukemia. Characterization of the RUNX1–PRDM16 fusion protein and comparison with the RUNX1–MDS1/EVI1 protein will facilitate the understanding of the mechanisms underlying RUNX1‐associated leukemia. © 2005 Wiley‐Liss, Inc.