title: Incidence of MLL rearrangement in acute myeloid leukemia, and a CALM-AF10 fusion in M4 type acute myeloblastic leukemia.
abstract: To determine the incidence of the mixed lineage leukemia (MLL) gene rearrangements in acute myeloid leukemia (AML) without cytogenetically-detected 11q23 abnormalities, we screened 64 cases of AML at diagnosis for MLL rearrangement by FISH. Three cases (4.7%) had a MLL rearrangement detected; one was shown to have a cryptic t(11;22)(q23;q11) and another to have a t(9;11)(p21-22;q23) which had been missed by the conventional cytogenetic study. No 11q23 structural abnormality was visible in the third case. Twenty-six of the 64 cases were further studied by Southern blotting and DNA hybridization, and four of these cases (15%) were found to have MLL rearrangement: in three of these, FISH had not detected any abnormality. FISH was also used to confirm MLL involvement in eight cases of AML that had a cytogenetic abnormality at 11q23; in one of these, Southern blot did not show a rearrangement. The survival of patients with MLL abnormalities identified by cytogenetics, FISH and/or DNA analysis was significantly worse than that of patients without MLL abnormalities (event-free survival p = 0.016) although two patients with a t(9;11)(p21-22;q23) were long-term survivors, consistent with this particular translocation having a better prognosis. One further case with a cytogenetic abnormality close to 11q23 was studied; it was found to have a t(10;11)(p13;q21), and the breakpoints were shown by FISH to involve the Clathrin Assembly Lymphoid Myeloid (CALM) gene at 11q21 and the AF10 gene at 10p13. Our data confirm the value of combining cytogenetic, FISH and molecular analyses to define the incidence and precise nature of MLL and 11q23 abnormalities in AML.
authors.affiliation: Academic Department of Haematology and Cytogenetics, The Institute of Cancer Research and The Royal Marsden NHS Trust, Sutton, Surrey, UK.
authors.forename: Said M H
authors.initials: SM
authors.lastname: Abdou
authors.forename: Dalal M
authors.initials: DM
authors.lastname: Jadayel
authors.forename: Toon
authors.initials: T
authors.lastname: Min
authors.forename: G John
authors.initials: GJ
authors.lastname: Swansbury
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Dainton
authors.forename: Osman
authors.initials: O
authors.lastname: Jafer
authors.forename: Ray L
authors.initials: RL
authors.lastname: Powles
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015139:Blotting, Southern / Q000592:standards; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D002879:Chromosomes, Human, Pair 10; D002880:Chromosomes, Human, Pair 11; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000592:standards; D015994:Incidence; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D011519:Proto-Oncogenes; D016019:Survival Analysis; D017741:Survivors; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: C114359:AF10-CALM fusion protein, human; D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase