Three-way translocation involves MLL, MLLT3, and a novel cell cycle control gene, FLJ10374, in the pathogenesis of acute myeloid leukemia with t(9;11;19)(p22;q23;p13.3)

• Type: Article in International Scientific Journal
• Date: 2006

Authors

Vieira, L (Author) Other; Sousa, AC (Author) Other; Matos, P (Author) Other; Marques, B (Author) Other; Alaiz, H (Author) Other; Ribeiro, MJ (Author) Other; Braga, P (Author) Other; da Silva, MG (Author) Other; Jordan, P (Author) Other

Journal

Title: Genes Chromosomes and Cancer

Vol. 45

Pages: 455-469

ISSN: 1045-2257

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 8 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-004-KXY

DOI: 10.1002/gcc.20311

Abstract (EN): The MLL gene, at 11q23, undergoes chromosomal translocation with a large number of partner genes in both acute lymphoblastic and acute myeloid leukemia (AML). We report a novel t(9; 11; 1 9)(p22;q23;p 13.3) disrupting MLL in an infant AML patient. The 5' end of MLL fused to chromosome 9 sequences on the der(11), whereas the 3' end was translocated to chromosome 19. We developed long-distance inverse-polymerase chain reaction assays to investigate the localization of the breakpoints on der(I 1) and der(19). We found that intron 5 of MILL was fused to intron 5 of MLLT3 at the der(11) genomic breakpoint, resulting in a novel in-frame MLL exon 5-MLLT3 exon 6 fusion transcript. On the der(19), a novel gene annotated as FLJ10374 was disrupted by the breakpoint. Using reverse transcription-polymerase chain reaction analysis, we showed that FLJ 103 74 is ubiquitously expressed in human cells. Transfection of the FLJ10374 protein in different cell lines revealed that it localized exclusively to the nucleus. In serum-starved NIH-3T3 cells, the expression of FLJ10374 decreased the rate of the G1-to-S transition of the cell cycle,whereas the suppression of FLJ10374 through short interfering RNA increased cell proliferation. These results indicate that FLJ 10374 negatively regulates cell cycle progression and proliferation. Thus, a single chromosomal rearrangement resulting in formation of the MLL-MLLT3 fusion gene and haplo-insufficiency of FLJ10374 may have cooperated to promote leukemogenesis in AML with t(9; 11; 19). (c) 2006 Wiley-Liss, Inc.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 15