CD10- pre-B acute lymphoblastic leukemia (ALL) is 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)

Abstract

, for the GMALL Study GroupImmunophenotyping disclosed CD10 negativity in 70 of 2408 cases of B-lineage acute lymphoblastic leukemia (ALL), although other criteria followed classification of pre-B ALL (eg, 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 or an 11q23/MLL rearrangement or both were evident in 46 of 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 IntroductionImmunologic subtyping and molecular genetic analysis allow riskadapted treatment of acute lymphoblastic leukemia (ALL). One poorprognosis subgroup of adult B-lineage precursor ALL is characterized by translocations involving the mixed lineage leukemia (MLL) gene on chromosome 11q23. These translocations occur in approximately 3% to 6% of all adult ALL and correlate with a younger age, a higher leukocyte count, and a CD19 ϩ /CD10 Ϫ /cytoplasmic(cy)IgM Ϫ immunophenotype (pro-B ALL) coexpressing myeloid marker. [1][2][3] Recent reports have shown that 11q23 translocations occur in up to 8% of T-ALLs, which were characterized by a poor clinical outcome. 4,5 Here, we present evidence of another high-risk group with frequent MLL gene translocations involving 82% (46 or 56) of the distinct CD19 ϩ /CD10 Ϫ /cyIgM ϩ pre-B ALL subset. Study designDual-staining immunophenotyping of 3168 newly diagnosed ALL specimens was performed with commercially available fluorochrome monoclonal antibody conjugates (Dako, Hamburg, Germany; BD Biosciences, San Jose, CA; BeckmanCoulter, Fullerton, CA) identifying pro-B ALL, TdT ϩ /CD19 ϩ /CD10 Ϫ /cyIgM Ϫ / surface(S)Ig Ϫ ; c-ALL, TdT ϩ /CD19 ϩ /CD10 ϩ /cyIgM Ϫ /SIg Ϫ ; and pre-B ALL, TdT ϩ /CD19 ϩ /CD10 ϩ /cyIgM ϩ /SIg Ϫ . 1,6,7 Ambiguous cases of CD10 ϩ B-lineage marker-positive blasts (5%-15% CD10 positivity) were rechecked by a second antibody (BD Biosciences, Dako). Only consistently negative samples (Ͻ 20% positive cells) were considered for CD10 negativity. Molecular detection of MLL-AF4 and BCR-ABL fusion as well as cytogenetic analysis were carried out as described elsewhere. [6][7][8][9][10][11] Fluorescence in situ hybridization (FISH) used directly labeled dual-color break-apart MLL rearrangement probes (Vysis, Downers Grove, IL). 7 At least 200 nuclei were scored, setting the cut-off value for false-positive nuclei at 10%. Patients were treated according the German Multicenter Adult ALL (GMALL) trials, 1,6,12 allocating MLL-AF4 ϩ patients to the high-risk arm. 13 The median follow-up was 25.6 months (range, 1.8-70.4 months) for survivors. The protocols were reviewed and approved by institutional review boards at each of the participating sites, and all patients provided informed consent prior to enrollment. Results and di...

Mixed Lineage Leukemia–Rearranged Childhood Pro-B and CD10-Negative Pre-B Acute Lymphoblastic Leukemia Constitute a Distinct Clinical Entity

“…Indeed, a few studies indicated that the cyIgM+/CD10À phenotype may be associated with MLL aberrations. However, except for a recent study by Gleissner et al (13) in adult ALL, none of these studies pointed out that the lack of CD10 expression may discriminate between MLL-rearranged and nonrearranged pre-B ALL cases (4 -7, 13, 37).…”

“…Although the topic of MLL in other than the pro-B ALL subset has been recently addressed in adult BCP ALL, data on the frequency and type of MLL aberrations in childhood common ALL (cALL) or pre-B ALL are scarce (13).…”

Methylation of the hTERT Promoter: A Novel Cancer Biomarker for Leptomeningeal Metastasis Detection in Cerebrospinal Fluids

“…Indeed, we have previously shown that these lymphoproliferative tumors are rarely hTERT hypermethylated (23). Furthermore, other sensitive tests, such as clonal B-cell gene rearrangement analysis, are easily available (31,32).…”

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

“…Expression of CD24 was not required for the diagnosis of a pro-B ALL, as CD24 frequently shows attenuated or absent expression in pro-B ALL. 9 CD10 Ϫ pre-B-ALL was diagnosed as outlined by Gleissner et al 12 Coexpression of B-lineage and myeloid antigens (CD13, CD33, CD65s, CD15) was confirmed in dual staining experiments in the majority of samples and, in a few samples with limited cell numbers for immunophenotypic analyses, by a greater than or equal to 20% overlap of CD19 positivity and expression of the respective myeloid antigen. The great majority of samples showed a very high cell count and more than 50% leukemic cells.…”