Abstract
The mixed lineage leukemia (MLL) gene located at chromosome band 11q23 is frequently rearranged in patients with therapy-related acute monocytic leukemia who received topoisomerase II inhibitors. We have identified a novel fusion partner of MLL (FAB M5b) in a patient who developed t-AML 9 years after treatment for acute lymphoblastic leukemia (ALL). The leukemic cells had a sole karyotypic abnormality of t(3;11) (p21;q23). Screening of a genomic DNA library, prepared from leukemic cell DNA, identified rearranged clones composed of MLL and a novel gene on chromosome 3p21 (AF3p21). The AF3p21 gene encodes a protein of 722 amino acids, which contains an Src homology 3 (SH3) domain, a proline-rich domain, and a bipartite nuclear localizing signal (NLS). RNA analysis demonstrated that exon 6 of the MLL gene fused to exon 2 of the AF3p21 gene. The resulting chimeric protein consists of AT-hooks, methyltransferase, and transcription repressor domains of MLL in addition to the AF3p21 proline-rich domain and NLS but not the AF3p21 SH3 domain.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Adolescent
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Amino Acid Sequence
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Base Sequence
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Bone Marrow Transplantation
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Combined Modality Therapy
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Cyclophosphamide / administration & dosage
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Cyclophosphamide / adverse effects
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DNA, Complementary / genetics
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Daunorubicin / administration & dosage
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Daunorubicin / adverse effects
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Etoposide / administration & dosage
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Etoposide / adverse effects
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Female
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Humans
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Leukemia, Monocytic, Acute / chemically induced
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Leukemia, Monocytic, Acute / drug therapy
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Leukemia, Monocytic, Acute / genetics*
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Leukemia, Monocytic, Acute / therapy
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Leukemia-Lymphoma, Adult T-Cell / drug therapy
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Molecular Sequence Data
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Muscle Proteins*
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Myeloid-Lymphoid Leukemia Protein
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Neoplasms, Second Primary / chemically induced
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Neoplasms, Second Primary / drug therapy
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Neoplasms, Second Primary / genetics*
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Neoplasms, Second Primary / therapy
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Nitrosourea Compounds / administration & dosage
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Nitrosourea Compounds / adverse effects
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Nuclear Proteins / genetics*
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Oncogene Proteins, Fusion / genetics*
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Sequence Alignment
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Sequence Homology, Nucleic Acid
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src Homology Domains / genetics*
Substances
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AF3p21-MLL fusion protein, human
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Adaptor Proteins, Signal Transducing
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DNA, Complementary
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Muscle Proteins
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NCKIPSD protein, human
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Nitrosourea Compounds
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Nuclear Proteins
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Oncogene Proteins, Fusion
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Myeloid-Lymphoid Leukemia Protein
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Etoposide
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Cyclophosphamide
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ranimustine
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Daunorubicin