A novel gene, AF1q, fused to MLL in t(1;11) (q21;q23), is specifically expressed in leukemic and immature hematopoietic cells.
Translocations involving chromosomal band 11q23 are associated with leukemias. These translocations fuse the MLL, a gene with sequence homology to the Drosophila trithorax, to genes from a number of other chromosomal loci. We have characterized two t(1;11)(q21;q23) translocations that fuse the MLL gene to a novel gene, AF1q on chromosomal band 1q21, in two infants with acute myelomonocytic leukemia (AMMOL). In one of these patients, der(11) represents an inframe fusion of the N-terminal portion of MLL gene to the complete AF1q open reading frame, whereas der(1) does not give rise to an open reading frame. This observation suggests that the N-terminal portion of MLL gene is critical for leukemogenesis in translocations involving band 11q23. The predicted wild-type AF-1q product is a 9-kD protein with no similarity to any other protein in the data banks. The AF1q mRNA is highly expressed in the thymus but not in peripheral lymphoid tissues. In contrast to its restricted distribution in normal hematopoietic tissue, AF1q was expressed in all leukemic cell lines tested.
Tse
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Division of Immunology/Cancer Research and Medical Genetics, Hospital for Sick Children, Toronto, Ontario, Canada.
Zhu
W
W
Chen
H S
HS
Cohen
A
A
D000595:Amino Acid Sequence; D001483:Base Sequence; D001798:Blood Proteins / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D002878:Chromosomes, Human, Pair 1; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D004247:DNA / Q000097:blood / Q000302:isolation & purification; D018076:DNA, Complementary / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D016366:Open Reading Frames; D011518:Proto-Oncogene Proteins; D011519:Proto-Oncogenes; D015183:Restriction Mapping; D014157:Transcription Factors; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D001798:Blood Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C091736:MLLT11 protein, human; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D004247:DNA; D011495:Histone-Lysine N-Methyltransferase