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The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia - results from the GMALL study group.

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Reinhardt,  Richard
High Throughput Technologies, Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Burmeister, T., Meyer, C., Schwartz, S., Hofmann, J., Molkentin, M., Kowarz, E., et al. (2009). The MLL recombinome of adult CD10-negative B-cell precursor acute lymphoblastic leukemia - results from the GMALL study group. Blood, 113(17), 4011--4015. doi:10.1182/blood-2008-10-183483.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0010-7DB0-B
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. The clinical studies are registered at http://www.clinicaltrials.gov as NCT00199056 [ClinicalTrials.gov] and NCT00198991 [ClinicalTrials.gov] .