Programmed Death Ligand-1 is Frequently Expressed in Primary Acute Myeloid Leukemia and B-Acute Lymphoblastic Leukemia.

BACKGROUND: The introduction of checkpoint inhibitors in solid cancer therapy showed successful results. The role of Programmed Death-1/Programmed Death-Ligand 1 (PD1/PD-L1) in hematologic malignancies is currently being investigated and clinical trials are ongoing. Preliminary findings showed conflicting results. In this study, we examined the degree of PD-L1 and PD-L2 expression in primary acute leukemia patients. METHODS: Flow cytometry expression of PD-L1 and PD-L2 was evaluated in de novo acute leukemia in the collaborating institutions between 2018 - 2020. RESULTS: One hundred forty patients were identified. PD-L1 was positive in 34/70 (49%) of AML, 25/50 (50%) of B-ALL, and none (0/20) of T-ALL patients. In contrast, PD-L2 was solely expressed in eight (19%) AML patients. The expression of PD-L1 showed statistically significant correlation with the type of acute leukemia (AML and B-ALL > T-ALL, p < 0.001) and with age group (adults > children, p = 0.048), but not with blast count, immunophenotype or cytogenetic mutations. The positivity for PD-L1 was associated with worse overall survival in AML, but not in B-ALL. CONCLUSIONS: The expression of PD-L1 is common among newly diagnosed AML and B-ALL patients and is not restricted to relapsed cases as previously described. PD-L2 is less commonly expressed and is accompanied by PD-L1 expression. Positive PD-L1 patients may benefit from treatment with immune checkpoint inhibitors, especially in AML. Further studies are recommended.

Flow cytometric signature of CD371-positive B-cell acute lymphoblastic leukemia.

OBJECTIVES: Multiparametric flow cytometry (MFC) aids in the diagnosis and management of B-cell acute lymphoblastic leukemia (B-ALL) by establishing a baseline immunophenotype for leukemic cells and measuring minimal residual disease (MRD) throughout the course of treatment. Aberrant expression patterns of myeloid markers in B-ALL are also examined during long-term surveillance. Here, we investigated the utility of the newly described myeloid marker cluster of differentiation (CD)371 in MRD surveillance via MFC in patients with CD371-positive B-ALL. METHODS: Eight-color MFC with standard panels (including CD371) was used to evaluate 238 patients with newly diagnosed B-ALL. Expression levels of key markers were retrospectively assessed at diagnosis, as well as days 15 and 33 of therapy. RESULTS: CD371 was expressed in 8.4% of patients with B-ALL. CD371 positivity was associated with older age at diagnosis, higher expression levels of CD34 and CD38, and lower expression levels of CD10 and CD20. Residual leukemic cells demonstrated decreased CD10 expression and increased CD45 expression after therapy, whereas CD371 expression remained stable. CONCLUSIONS: Patients with CD371-positive B-ALL exhibit a specific signature that merits further analysis, particularly because it has been associated with DUX4 rearrangement.