title: Cryptic insertion of MLL gene into 9p22 leads to MLL-MLLT3 (AF9) fusion in a case of acute myelogenous leukemia.
abstract: The formation of a leukemogenic fusion product in hematopoietic malignancies is commonly achieved by chromosomal translocation. Alternate and cytogenetically undetectable mechanisms of fusion transcript generation have been documented for BCR-AB1, AML1-ETO, PML-RARA, NPM/ALK, and MLL-MLLT2 (AF4). Here, we report the investigation of a cryptic rearrangement leading to MLL-MLLT3 transcript formation. Cytogenetic analysis of peripheral blood from a 50-year-old acute myeloid leukemia patient yielded a karyotype of 47,XY,+8,del(11)(q21q23) in all metaphase cells examined. Metaphase fluorescence in situ hybridization analysis using the MLL probe at 11q23 revealed that the 5' portion of the MLL gene was inserted into chromosome 9 at band p22, whereas the 3' region of the MLL gene remained on chromosome 11. Whole-chromosome paint analysis confirmed the cryptic transfer of chromosome 11 material to 9p22. With this information, the karyotype was reassigned as 47,XY,+8,der(9)ins(9;11)(p22;q23q23),del(11)(q21q23). RT-PCR was used to show that the cryptic rearrangement in this patient led to the fusion of the MLL and MLLT3 transcripts on the der(9). The presence of the MLL-MLLT3 transcript is consistent with the clinical findings in this patient.
authors.affiliation: Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: Shago
authors.forename: Derek
authors.initials: D
authors.lastname: Bouman
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: Mark
authors.initials: M
authors.lastname: Minden
authors.forename: Kathy
authors.initials: K
authors.lastname: Chun
mesh_terms: D000208:Acute Disease; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional / Q000235:genetics*; D051788:Myeloid-Lymphoid Leukemia Protein; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011519:Proto-Oncogenes; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; C497422:KMT2A protein, human; C474558:MLL-AF9 fusion protein, human; C529663:MLL-MLLT3 fusion protein, human; D015514:Oncogene Proteins, Fusion; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase