title: Screening for mutations of Bcl10 in leukaemia.
abstract: The Bcl10 gene was identified through characterization of the t(1;14)(p22;q32) associated with mucosa-associated lymphoid tissue (MALT) lymphoma. Bcl10 is implicated in the regulation of apoptosis and has been reported to be mutated in other subtypes of non-Hodgkin's B-cell lymphoma (B-NHL) and leukaemic cell lines, raising the possibility that its deregulation could be implicated in other forms of haematological malignancy. We screened 226 cases, including 123 acute myeloid leukaemia (AML), 50 acute lymphoblastic leukaemia (ALL), 20 chronic myeloid leukaemia (CML), 10 chronic lymphocytic leukaemia-prolymphocytic leukaemia (CLL/PLL) and 23 cases with 1p abnormalities, for Bcl10 mutations by reverse transcription polymerase chain reaction-single-stranded conformation polymorphism (RT-PCR/SSCP). Three known polymorphisms and two common splice variants were identified; however, no mutations were detected. One splice variant led to a 33-bp in frame deletion, whereas the other caused a 16-bp deletion predicting C-terminal truncation of Bcl10. However, both splice variants were also detected in normal bone marrow, suggesting that they are unlikely to be of pathogenetic significance. Furthermore, Southern blot analysis revealed no rearrangements of Bcl10 among 16 ALL and 11 cases of haematological malignancy with 1p abnormalities. Our results suggest that mutation of the Bcl10 gene as a mechanism of tumorigenesis is not associated with leukaemia.
authors.affiliation: Division of Medical and Molecular Genetics, Guy's, King's and St. Thomas' School of Medicine, London, UK. david.grimwade@kcl.ac.uk
authors.forename: D
authors.initials: D
authors.lastname: Grimwade
authors.forename: M Q
authors.initials: MQ
authors.lastname: Du
authors.forename: S
authors.initials: S
authors.lastname: Langabeer
authors.forename: J
authors.initials: J
authors.lastname: Rogers
authors.forename: E
authors.initials: E
authors.lastname: Solomon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D000074018:B-Cell CLL-Lymphoma 10 Protein; D015139:Blotting, Southern; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D007951:Leukemia, Myeloid / Q000235:genetics; D015463:Leukemia, Prolymphocytic / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D009363:Neoplasm Proteins