Open AccessAF5q31 , a newly identified AF4 -related gene, is fused to MLL in infant acute lymphoblastic leukemia with ins(5;11)(q31;q13q23)
Author(s) -
Tomohiko Taki,
Hiroki Kano,
Masafumi Taniwaki,
Masahiro Shinoda,
Masayoshi Yamaguchi,
Yasuhide Hayashi
Publication year - 1999
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.96.25.14535
Subject(s) - biology , chromosomal translocation , transactivation , fusion protein , fusion gene , genetics , exon , phenotype , gene , homologous chromosome , microbiology and biotechnology , gene expression , recombinant dna
Infant acute lymphoblastic leukemia (ALL) withMLL gene rearrangements is characterized by early pre-B phenotype (CD10− /CD19+ ) and poor treatment outcome. The t(4;11), creatingMLL-AF4 chimeric transcripts, is the predominant 11q23 chromosome translocation in infant ALL and is associated with extremely poor prognosis as compared with other 11q23 translocations. We analyzed an infant early preB ALL with ins(5;11)(q31;q13q23) and identified theAF5q31 gene on chromosome 5q31 as a fusion partner of theMLL gene. TheAF5q31 gene, which encoded a protein of 1,163 aa, was located in the vicinity of the cytokine cluster region of chromosome 5q31 and contained at least 16 exons. TheAF5q31 gene was expressed in fetal heart, lung, and brain at relatively high levels and fetal liver at a low level, but the expression in these tissues decreased in adults. The AF5q31 protein was homologous to AF4-related proteins, including AF4, LAF4, and FMR2. The AF5q31 and AF4 proteins had three homologous regions, including the transactivation domain of AF4, and the breakpoint of AF5q31 was located within the region homologous to the transactivation domain of AF4. Furthermore, the clinical features of this patient with theMLL-AF5q31 fusion transcript, characterized by the early pre-B phenotype (CD10− /CD19+ ) and poor outcome, were similar to those of patients havingMLL-AF4 chimeric transcripts. These findings suggest that AF5q31 and AF4 might define a new family particularly involved in the pathogenesis of 11q23-associated-ALL.