title: Complex and cryptic chromosomal rearrangements involving the MLL gene in acute leukemia: a study of 7 patients and review of the literature.
abstract: Chromosomal rearrangements involving the MLL gene have been associated with many different types of hematological malignancies. Most of them are easily recognized by conventional cytogenetics. However, in some cases, complex, unusual or cryptic rearrangements make the MLL involvement difficult or impossible to be detected by conventional cytogenetics. Fluorescent in situ hybridization with a panel of probes coupled with long distance inverse-PCR was used to identify chromosomal rearrangements involving the MLL gene. Seven unusual chromosomal rearrangements were identified, including two complex translocations, three insertions of material of chromosome 11 in another chromosome and one insertion of chromosome material into the MLL gene. Conventional cytogenetics showed three patients to have a deletion of 11q; one had an unexpected t(6;11)(q27;q23) whereas the other two patients had also an insertion of MLL material in another chromosome. Concurrent 3' deletion in the MLL rearrangement was observed in two patients. We recommend a systematic approach to be used in all cases of acute leukemia starting with FISH analyses using a commercially available MLL split signal probe. Should an abnormality be discovered, the analysis has to be completed by further molecular cytogenetic and genomic PCR methods in order to unravel the recombination mechanism.
authors.affiliation: Université de Brest, Faculté de Médecine et des Sciences de la Santé, Brest, France. marc.debraekeleer@univ-brest.fr <marc.debraekeleer@univ-brest.fr>
authors.forename: Etienne
authors.initials: E
authors.lastname: De Braekeleer
authors.forename: Claus
authors.initials: C
authors.lastname: Meyer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Douet-Guilbert
authors.forename: Frédéric
authors.initials: F
authors.lastname: Morel
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Le Bris
authors.forename: Christian
authors.initials: C
authors.lastname: Berthou
authors.forename: Bertrand
authors.initials: B
authors.lastname: Arnaud
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
authors.forename: Claude
authors.initials: C
authors.lastname: Férec
authors.forename: Marc
authors.initials: M
authors.lastname: De Braekeleer
mesh_terms: D000208:Acute Disease; D000230:Adenocarcinoma; D000328:Adult; D000368:Aged; D001752:Blast Crisis / Q000235:genetics; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics / Q000648:ultrastructure; D004379:Duodenal Neoplasms; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007938:Leukemia / Q000235:genetics* / Q000473:pathology; D007948:Leukemia, Monocytic, Acute / Q000151:congenital / Q000235:genetics; D015479:Leukemia, Myelomonocytic, Acute / Q000235:genetics; D015477:Leukemia, Myelomonocytic, Chronic / Q000473:pathology; D008297:Male; D016254:Mutagenesis, Insertional; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics; D011471:Prostatic Neoplasms; D017384:Sequence Deletion; D014178:Translocation, Genetic
chemical_list: C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase