AF4p12, a human homologue to the furry gene of Drosophila, as a novel MLL fusion partner.

Abstract:

:More than 35 different partner genes with the mixed lineage leukemia (MLL) gene have been cloned from leukemia cells with translocations involving chromosome 11 band q23. In this study, we report on a novel fusion partner of the MLL gene, AF4p12, which we have identified as the human homologue to the furry gene of Drosophila. AF4p12, highly conserved in evolution, encodes a large protein of 3,105 amino acids. The expression of AF4p12 has been preferentially detected in colon, placenta, and brain tissues and in tumor cells of lymphoid origin. We show that the t(4;11)(p12;q23) translocation results in the creation of a chimeric RNA encoding a putative fusion protein containing 1,362 amino acids from the NH2-terminal part of MLL and 712 amino acids from the COOH-terminal part of AF4p12. FLT3 and HOXA9 genes are overexpressed in this leukemia. We found that the COOH-terminal part of AF4p12 fused to MLL contains a leucine zipper motif and exhibits transcriptional activation properties when fused to Gal4 DNA-binding domains in transient transfection assays. The AF4p12 fragment fused to MLL may contribute to the oncogenic activation of MLL, possibly through specific recruitment of the transcriptional machinery.

journal_name

Cancer Res

journal_title

Cancer research

authors

Hayette S,Cornillet-Lefebvre P,Tigaud I,Struski S,Forissier S,Berchet A,Doll D,Gillot L,Brahim W,Delabesse E,Magaud JP,Rimokh R

doi

10.1158/0008-5472.CAN-05-1325

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

6521-5

issue

15

eissn

0008-5472

issn

1538-7445

pii

65/15/6521

journal_volume

65

pub_type

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