A Novel Gene, AF1q, Fused to MLL in t(1; 11)(q21;q23), Is Specifically Expressed in Leukemic and Immature Hematopoietic Cells

• Published in: Blood 1995-02, Vol.85 (3), p.650-656
• Main Authors: Tse, William, Zhu, Weimin, Chen, Hai Shiene, Cohen, Amos
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Blood Proteins - biosynthesis; Blood Proteins - genetics; Cell Line; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 11; Cloning, Molecular; DNA - blood; DNA - isolation & purification; DNA, Complementary - chemistry; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Gene Expression; Hematologic and hematopoietic diseases; Hematopoietic Stem Cells - metabolism; Histone-Lysine N-Methyltransferase; Humans; Leukemia - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Molecular Sequence Data; Myeloid-Lymphoid Leukemia Protein; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Open Reading Frames; Proto-Oncogene Proteins; Proto-Oncogenes; Restriction Mapping; Transcription Factors; Translocation, Genetic; Tumor Cells, Cultured; Zinc Fingers
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V85.3.650.bloodjournal853650

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 in-frame 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.