AF4p12, a human homologue to the furry gene of Drosophila, as a novel MLL fusion partner.
نویسندگان
چکیده
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.
منابع مشابه
t(11;14)(q23;q24) generates an MLL-human gephyrin fusion gene along with a de facto truncated MLL in acute monoblastic leukemia.
More than 20 different partner genes with MLL have been cloned from leukemia cells with translocations involving chromosome 11 band q23 (11q23). All reported partner genes fused in-frame to MLL and the fusion cDNA encode chimeric MLL proteins with a significant portion derived from the partner genes. We analyzed one patient with de novo acute monoblastic leukemia with t(11;14)(q23;q24) and iden...
متن کاملEtoposide induces chimeric Mll gene fusions.
MLL gene fusions are the hallmark of more than 70% of therapy-related leukemias (t-ML) associated with topoisomerase II inhibitors (e.g., etoposide) and cause leukemia in murine transgenic models. To determine whether Mll genomic fusions can occur after exposure to topoisomerase II inhibitors, we developed a long-distance inverse PCR DNA-based assay for chimeric Mll fusions in mouse embryonic s...
متن کاملAF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily.
Fusion genes implicating the MLL gene have been recently demonstrated in various 11q23 chromosomal abnormalities in human hematopoietic malignancies. We analyzed a t(6;11)(q21;q23) translocation detected in a secondary acute myeloblastic leukemia. This translocation results in fusion of the MLL gene on 11q23 to a previously unknown gene on chromosome 6 that differs from the previously reported ...
متن کاملHOX GENES: Seductive Science, Mysterious Mechanisms
HOX genes are evolutionarily highly conserved. The HOX proteins which they encode are master regulators of embryonic development and continue to be expressed throughout postnatal life. The 39 human HOX genes are located in four clusters (A-D) on different chromosomes at 7p15, 17q21 [corrected] 12q13, and 2q31 respectively and are assumed to have arisen by duplication and divergence from a primo...
متن کاملAF 6 q 21 , a Novel Partner of the MLL Gene in t ( 6 ; 11 ) ( q 21 ; q 23 ) , Defines a Forkhead Transcriptional
Fusion genes implicating the MLL gene have been recently FH family members whose genes are already known to be demonstrated in various 11q23 chromosomal abnormalities involved in chromosomal translocations of human maligin human hematopoietic malignancies. We analyzed a nancies, AFX and FKHR. Strikingly, in these translocations t(6;11)(q21;q23) translocation detected in a secondary acute the br...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Cancer research
دوره 65 15 شماره
صفحات -
تاریخ انتشار 2005