Purpose: Mixed lineage leukemia (MLL) abnormalities occur in f50% of childhood pro-B acute lymphoblastic leukemia (ALL). However, the incidence and type of MLL rearrangements have not been determined in common ALL (cALL) and CD10+ or CD10À pre-B ALL. Experimental Design: To address this question, we analyzed 29 patients with pro-B ALL, 11patients with CD10À pre-B ALL, 23 pre-B, and 26 cALL patients with CD10 on 20% to 80%, as well as 136 pre-B and 143 cALL patients with CD10 z80% of blasts. They were all enrolled in four Austrian ALL multicenter trials. Conventional cytogenetics were done to detect 11q23 abnormalities and in parallel the potential involvement of the MLL gene was evaluated with a split apart fluorescence in situ hybridization probe set. Results:We found that15 of 29 pro-B ALL, 7 of11CD10À pre-B ALL, and1of 2 French-AmericanBritish classification L1 mature B-cell leukemia cases had a MLL rearrangement. However, no 11q23/MLL translocation was identified among the CD10+ pre-B and cALL patients. MLL-rearranged pro-B and CD10À pre-B ALL cases had similar clinical and immunophenotypic (coexpression of CDw65 and CD15) features at initial diagnosis. Conclusions: The striking similarities between the two CD10À ALL subsets imply that CD10À pre-B ALL variants may represent pro-B ALL cases that maintained the propensity to rearrange and express their immunoglobulin heavy chain rather than actual pre-B ALL forms transformed at this later stage of B-cell differentiation. However, direct experimental data are needed to confirm this observation.Rearrangements involving the mixed lineage leukemia (MLL) gene on chromosome band 11q23 represent nonrandom chromosomal abnormalities commonly found in human hematologic malignancies, including both acute lymphoblastic leukemia (ALL; 5-10%) and acute myeloid leukemia (AML; 5%; refs. 1, 2). Although the exact function of the MLL gene is unclear, it displays intrinsic histone methyltransferase activity and is known to play an important role in maintaining a cell type -specific expression of HOX genes, which are necessary for the cellular differentiation process (2, 3).According to most published series, MLL-rearranged B-cell precursor (BCP) ALL can be reliably identified by a distinct immature CD10À/CD24À phenotype that is commonly characterized by the concurrent expression of the myeloid markers CDw65 and CD15, and of the chondroitin sulfate proteoglycan neuron-glial antigen 2 (NG2; refs. 4 -7). Due to the observation that the translocation t(4;11) with its molecular counterpart, the MLL/AF4 fusion gene, is the most frequent MLL-specific aberration in infants with pro-B ALL, the CD10 negativity of MLL-rearranged BCP leukemia is commonly regarded as a sign of cellular immaturity (2,8,9). Furthermore, the coexpression of CDw65 and CD15 is taken as an evidence that this type of leukemia even represents a transformed upstream lymphomyelomonocytic progenitor cell.As recent collaborative studies showed a marked clinical heterogeneity among MLL-rearranged ALL requiring d...

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