title: Involvement of the MLL gene in adult T-lymphoblastic leukemia.
abstract: While the MLL "recombinome" is relatively well characterized in B-cell precursor acute lymphoblastic leukemia (BCP ALL), available data for adult acute T-lymphoblastic leukemia (T-ALL) are scarce. We performed fluorescence in situ hybridization (FISH) for an MLL split signal on 223 adult T-ALL samples obtained within the framework of the German Multicenter ALL 07/2003 therapy trial. Three biphenotypic leukemias (T-ALL/AML) were also included in the analysis. Samples showing any alteration by FISH were further investigated to characterize the MLL aberration. In addition, they were investigated for common genetic lesions known in T-ALL. Twenty-two cases (9.5%) showed an abnormal MLL signal by FISH analysis. Most of these appeared to be deletions or gains but in five cases (2.1%) a chromosomal translocation involving the MLL gene was identified. The translocation partners and chromosomal breakpoints were molecularly characterized. Three T-ALLs had an MLL-AF6/t(6;11) and two biphenotypic leukemias had an MLL-ELL/t(11;19). The chromosomal breakpoints in two of the MLL-AF6-positive cases were located outside the classical MLL major breakpoint cluster known from BCP ALL. In conclusion, the spectrum of MLL translocation partners in adult T-ALL much more resembles that of AML than that of BCP ALL and thus the mechanisms by which MLL contributes to leukemogenesis in adult T-ALL appear to differ from those in BCP ALL. Proposals are made for the diagnostic assessment of MLL fusion genes in adult T-ALL.
authors.affiliation: Labor Berlin, Abteilung Tumorzytogenetik, Berlin, Germany.
authors.forename: Seval
authors.initials: S
authors.lastname: Türkmen
authors.forename: Bernd
authors.initials: B
authors.lastname: Timmermann
authors.forename: Gesine
authors.initials: G
authors.lastname: Bartels
authors.forename: Daniela
authors.initials: D
authors.lastname: Gröger
authors.forename: Claus
authors.initials: C
authors.lastname: Meyer
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwartz
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Harald
authors.initials: H
authors.lastname: Rieder
authors.forename: Nicola
authors.initials: N
authors.lastname: Gökbuget
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
authors.forename: Thomas
authors.initials: T
authors.lastname: Burmeister
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D056726:Genetic Association Studies; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: C497422:KMT2A protein, human; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase