AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14)

Frequent expression of new cancer/testis gene D40/AF15q14 in lung cancers of smokers

“…In the later stage of this study, however, it turned out that the sequence of D40 is identical with that of the gene AF15q14 (Hayette et al, 2000), except for the 3' end and several nucleotides. The nucleotide sequence in D40 cDNA revealed in this study was deposited in GenBank/EMBL/DDBJ (accession no: AB022190).…”

“…A sequence homology search revealed that the D40 sequence is the same as that of the AF15q14 gene (Hayette et al, 2000). This gene is a partner that fuses with MLL, an oncogenic gene involved in the development of acute leukaemia (Hunger et al, 1993;Thirman et al, 1994;Hernandez et al, 1995;Dimartino and Cleary, 1999).…”

“…The above information could be quite important for characterising the CT genes and when considering the treatment of cancer patients with immunotherapy. As the carboxy terminal region of D40/AF15q14 protein contains a nuclear localisation signal, it may be a nuclear protein (Hayette et al, 2000). This protein may play important roles in gene regulation, such as at the levels of transcription and mRNA processing.…”

“…D40 protein binds to the latter. A sequence homology search revealed that D40 is the same gene as AF15q14 which was recently identified as one of the genes that fuses with an oncogenic gene MLL (mixed lineage leukaemia) in acute leukaemia (Hayette et al, 2000). While the D40 gene is barely expressed in normal tissues except for the testis, it is expressed frequently in various human cancer cell lines and primary tumours derived from differ-ent tissues and organs, suggesting that D40 is a novel member of the CT family.…”

MLL-SEPTIN6 fusion recurs in novel translocation of chromosomes 3, X, and 11 in infant acute myelomonocytic leukaemia and in t(X;11) in infant acute myeloid leukaemia, and MLL genomic breakpoint in complex MLL-SEPTIN6 rearrangement is a DNA topoisomerase II cleavage site

“…Several MLL fusions with nuclear transcription factors (Corral et al, 1996;Lavau et al, 1997) or with proteins central to transcriptional regulation (Lavau et al, 2000a,b) transform hematopoietic progenitors (Lavau et al, 1997(Lavau et al, , 2000a, and/or are leukaemogenic in transgenic mice (Corral et al, 1996) or in mouse models created by retroviral-mediated gene transfer (Lavau et al, 1997(Lavau et al, , 2000a. Whereas many MLL partner proteins have structural motifs of nuclear transcription factors (LAF-4, AF4, AF5a, AF5q31, AF6q21, AF9, AF10, MLL, AF17, ENL, AFX) Chaplin et al, 1995;Gu et al, 1992;Hillion et al, 1997;Morrissey et al, 1993;Nakamura et al, 1993;Prasad et al, 1994;Schichman et al, 1994;Taki et al, 1996Taki et al, , 1999aTkachuk et al, 1992), proteins involved in transcriptional regulation (CBP, ELL, p300) (Ida et al, 1997;Sobulo et al, 1997;Taki et al, 1997;Thirman et al, 1994) or, in one case, a nuclear protein of unknown function (AF15q14) (Hayette et al, 2000), other MLL partner proteins are found in the cytoplasm (AF1p, AF1q, AF3p21, GMPS, LPP, GRAF, FBP17, ABI-1, GAS7, EEN) (Bernard et al, 1994;Borkhardt et al, 2000;Daheron et al, 2001;Fuchs et al, 2001;Megonigal et al, 2000a;Pegram et al, 2000;Sano et al, 2000;So et al, 1997;Taki et al, 1998;Tse et al, 1995) or at the cell membrane (AF6, LARG, GPHN) (Eguchi et al, 2001;…”