CD10-negative pre-B acute lymphoblastic leukemia (ALL): a distinct high-risk subgroup of adult ALL associated with a high frequency of MLL aberrations. Results of the German Multicenter Trials for Adult ALL (GMALL) Running title: CD10-negative pre-B ALL

Immunophenotyping disclosed CD10 negativity in 70 of 2,408 cases of B-lineage acute lymphoblastic leukemia (ALL), although other criteria followed classification of pre-B ALL (e.g., cytoplasmic immunoglobulin positivity). These blasts showed high myeloid antigen expression (60% CD65-positivity) and reacted with antibody 7.1 in 95% of the cases. MLL-AF4 fusion transcripts and/or an 11q23/MLL rearrangement were evident in 46/56 samples (82%). Although 83% of the patients achieved complete remission, the remission duration remained remarkably low: 141 days for MLL-rearrangement-positive and 245 days for MLL-rearrangement-negative CD10 pre-B ALL. Thus the overall survival probability 3 years after diagnosis was 0.34 (± 0.20 SE) in MLL-rearrangement-negative versus 0.12 (± 0.06 SE) in MLLrearrangement-positive CD10 pre-B ALL. Our data identify CD10 cytoplasmic Ig-positive pre-B ALL as a rare (2.2%) but distinct immunosubtype of adult ALL that is characterized by a high MLL rearrangement rate and a worse outcome.