title: The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group.
abstract: MLL translocations in adult B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) are largely restricted to the immature CD10(-) immunophenotypes. MLL-AF4 is known to be the most frequent fusion transcript, but the exact frequencies of MLL aberrations in CD10(-) adult BCP-ALL are unknown. We present a genetic characterization of 184 BCR-ABL(-) CD10(-) adult ALL cases (156 cyIg(-), 28 cyIg(+)) diagnosed between 2001 and 2007 at the central diagnostic laboratory of the GMALL study group. Patient samples were investigated by RT-PCR for MLL-AF4, MLL-ENL, and MLL-AF9 and by long-distance inverse polymerase chain reaction, thus also allowing the identification of unknown MLL fusion partners at the genomic level. MLL-AF4 was detected in 101 (54.9%) and MLL-ENL in 11 (6.0%) cases. In addition, rare MLL fusion genes were found: 2 MLL-TET1 cases, not previously reported in ALL, 1 MLL-AF9, 1 MLL-PTD, a novel MLL-ACTN4, and an MLL-11q23 fusion. Chromosomal breakpoints were determined in all 118 positive cases, revealing 2 major breakpoint cluster regions in the MLL gene. Characteristic features of MLL(+) patients were significantly lower CD10 expression, expression of the NG2 antigen, a higher white blood count at diagnosis, and female sex. Proposals are made for diagnostic assessment.
authors.affiliation: Charité Universitätsmedizin Berlin, Campus Benjamin Franklin (CBF), Medizinische Klinik III, Berlin, Germany. thomas.burmeister@charite.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Burmeister
authors.forename: Claus
authors.initials: C
authors.lastname: Meyer
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwartz
authors.forename: Julia
authors.initials: J
authors.lastname: Hofmann
authors.forename: Mara
authors.initials: M
authors.lastname: Molkentin
authors.forename: Eric
authors.initials: E
authors.lastname: Kowarz
authors.forename: Björn
authors.initials: B
authors.lastname: Schneider
authors.forename: Thorsten
authors.initials: T
authors.lastname: Raff
authors.forename: Richard
authors.initials: R
authors.lastname: Reinhardt
authors.forename: Nicola
authors.initials: N
authors.lastname: Gökbuget
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
authors.forename: Rolf
authors.initials: R
authors.lastname: Marschalek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism*; D015260:Neprilysin / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D012955:Societies, Medical
chemical_list: C497422:KMT2A protein, human; D011993:Recombinant Fusion Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D015260:Neprilysin