The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia: results from the GMALL study group
Thomas Burmeister, Claus Meyer, Stefan Schwartz, Julia Hofmann, Mara Molkentin, Eric Kowarz, Björn Schneider, Thorsten Raff, Richard Reinhardt, Nicola Gökbuget, Dieter Hoelzer, Eckhard Thiel, Rolf Marschalek, Thomas Burmeister, Claus Meyer, Stefan Schwartz, Julia Hofmann, Mara Molkentin, Eric Kowarz, Björn Schneider, Thorsten Raff, Richard Reinhardt, Nicola Gökbuget, Dieter Hoelzer, Eckhard Thiel, Rolf Marschalek
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.
Trial registration: ClinicalTrials.gov NCT00198991 NCT00199056.
Source: PubMed