title: Incidence of c-Cbl mutations in human acute myeloid leukaemias in an Australian patient cohort.
abstract: OBJECTIVE
  The aim of this study was to investigate the incidence and characteristics of c-Cbl mutations in acute myeloid leukaemias (AMLs) from an Australian patient cohort. Two initial studies examining c-Cbl mutations in AML, one from Germany and one from the US, found vastly different incidences of mutations (0.6% compared to 33%, respectively). Therefore, it was important to determine the incidence and characteristics of c-Cbl mutations in a cohort of Australian AML patients.
  
  
  METHODS
  Ninety patients with AML were investigated. The open reading frame between exons 4 and 11 of the c-Cbl gene was analysed by reverse-transcription polymerase chain reaction (RT-PCR), nested PCR and DNA sequencing.
  
  
  RESULTS
  We found four AML samples (4/90; 4.44%) with distinct c-Cbl deletions involving exons 6 to 9. Sample 10 [AML with t(8;21)] showed two deletions [c.870-1007del] and [c.1106-1228del]. Sample 81 (AML with minimal differentiation) showed a large deletion [c.1008-1431del] causing a frameshift and a premature stop codon. Sample 82 (AML without maturation) showed two deletions [c.928-1307del] and [c.1385-1431del] also causing a frameshift and a premature stop codon. Sample 84 (AML with myelodysplasia related changes) showed a large deletion [c.964-1380del].
  
  
  CONCLUSIONS
  Although our data indicate that c-Cbl deletions are not common in AML in the Australian population, they do raise the possibility that c-Cbl mutations might contribute to the pathogenesis of these AML cases.
authors: Department of Haematology, PathWest Laboratory Medicine WA, Nedlands, WA 6009, Australia. Reza.Ghassemifar@health.wa.gov.au
authors: Reza
authors: R
authors: Ghassemifar
authors: Christine B F
authors: CB
authors: Thien
authors: Jill
authors: J
authors: Finlayson
authors: David
authors: D
authors: Joske
authors: Gavin M
authors: GM
authors: Cull
authors: Bradley
authors: B
authors: Augustson
authors: Wallace Y
authors: WY
authors: Langdon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D017353:Gene Deletion; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics*; D014904:Western Australia / Q000453:epidemiology; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm; D050721:Proto-Oncogene Proteins c-cbl; C067419:CBL protein, human