CO06 | Absent CD38 expression negatively impacts and further discriminates outcome on the high-risk subgroup Ph-like acute lymphoblastic leukemia

Introduction. Ph-like acute lymphoblastic leukemia (ALL) is a B-ALL subtype lacking BCR::ABL1 but sharing a transcriptomic profile similar to Ph+ ALL and being characterized by poor prognosis. Its genetic heterogeneity and lack of standardized diagnostic criteria hamper clinical management and risk stratification. Here we aimed at defining novel prognostic markers by integrating immunophenotypic and molecular data in adult B-lineage ALL.Methods. We retrospectively analyzed 207 newly diagnosed adults (18–65 yrs) with B-ALL devoid of major molecular aberrations (BCR::ABL1, TCF3::PBX1 and KMT2A) enrolled in the GIMEMA LAL1913, LAL2317 and ALL2922 trials (the latter designed specifically for Ph-like ALL). By applying the BCR/ABL1-like predictor (Chiaretti et al, BJH 2018), 70 cases were Ph-like and 137 were non-Ph-like (n=137). CNVs were assessed by MLPA and fusions by targeted RNA-seq.Results. At baseline, antigen expression levels were similar between the two entities by immunophenotypic analysis (Figure 1A). However, Ph-like ALL cases expressed lower CD38 (67.7% vs 92.6%, p