TP53 mutations are associated with impaired response and shorter survival in patients with CLL. Analysis of TP53 mutations should be performed in patients with CLL who have progressive disease before starting first-line treatment, and those with mutations should be selected for novel experimental therapies.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of leukemia/lymphoma, whose diagnosis can be difficult to achieve due to its clinical and biological heterogeneity, as well as its overlapping features with other hematologic malignancies. In this study we investigated whether the association between the maturational stage of tumor cells and the clinico-biological and prognostic features of the disease, based on the analysis of 46 BPDCN cases classified into three maturation-associated subgroups on immunophenotypic grounds. Our results show that blasts from cases with an immature plasmacytoid dendritic cell (pDC) phenotype exhibit an uncommon CD56− phenotype, coexisting with CD34+ non-pDC tumor cells, typically in the absence of extramedullary (e.g. skin) disease at presentation. Conversely, patients with a more mature blast cell phenotype more frequently displayed skin/extramedullary involvement and spread into secondary lymphoid tissues. Despite the dismal outcome, acute lymphoblastic leukemia-type therapy (with central nervous system prophylaxis) and/or allogeneic stem cell transplantation appeared to be the only effective therapies. Overall, our findings indicate that the maturational profile of pDC blasts in BPDCN is highly heterogeneous and translates into a wide clinical spectrum -from acute leukemia to mature lymphoma-like behavior-, which may also lead to variable diagnosis and treatment.

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Early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL), was first identified within cases of childhood T-ALL based on its unique immunophenotypic and genetic features of limited (early) T-cell differentiation associated with (some) myeloid and stem cell features. 1 Thus ETP-ALL blasts express CD7, dim CD5 (<75% positive cells), in the absence of CD1a and CD8, and positivity for ≥1 myeloid/stem cell related markers (i.e., CD34, CD13 or CD33). 1,2 In turn, ETP-ALL frequently shows myeloid-associated gene alterations such as FLT3, NRAS/KRAS, DNMT3A, IDH1 and IDH2 mutations, 3,4 with lower frequencies of other T-ALL-associated mutations (e.g., NOTCH1 and CDKN2A/B gene mutations). 5,6 The World Health Organization (WHO) 2016 classification of ALL included ETP-ALL for the first time, as a provisional entity, 7 but it failed to establish robust diagnostic criteria. Thus, after the first immunophenotypic characterization of ETP-ALL by Coustan-Smith et al. 1 the proposed criteria did not allow identification of all ETP-ALL cases as detected by gene expression profiling. 2 In addition, the "partial CD5 expression" criterion had a negative impact on the reproducibility of ETP-ALL diagnoses because of the lack of standardization of the method used for its assessment. Because of this, Zuubier et al. proposed refined immunophenotypic criteria by excluding CD5 expression while adding negativity for CD4. 2 From the clinical point of view early studies based on limited numbers of pediatric patients indicated that ETP-ALL was associated with a very poor outcome. 1,8,9 More recent data, based on larger series of children treated with more intensive therapy, showed no significant differences in outcome for ETP-ALL vs. other T-ALL cases. 10 In contrast, limited data have been reported for adult ETP-ALL, with conflicting results. 11,12 In one study, adult ETP-ALL was associated with a worse prognosis following different frontline chemotherapy schedules. 11 The