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

Blood. 2009 Apr 23;113(17):4011-5. doi: 10.1182/blood-2008-10-183483. Epub 2009 Jan 14.


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: NCT00198991 NCT00199056.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chromosomes, Human / genetics
  • Female
  • Histone-Lysine N-Methyltransferase
  • Humans
  • Male
  • Middle Aged
  • Myeloid-Lymphoid Leukemia Protein / genetics
  • Myeloid-Lymphoid Leukemia Protein / metabolism*
  • Neprilysin / metabolism
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Societies, Medical


  • KMT2A protein, human
  • Recombinant Fusion Proteins
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase
  • Neprilysin

Associated data