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While natural killer (NK) cells are essential players in detection and elimination of malignant cells, these surveillance properties can be compromised by cancer cells. Since NK cell education primarily occurs in the bone marrow and lymphoid tissue, this process might be particularly affected by their infiltration with lymphoma cells. This study aimed to explore functional properties of diffuse large B-cell lymphoma (DLBCL) patient NK cells, which could potentially promote tumour immune evasion and disease propagation.NK cells isolated from the peripheral blood (PB) of 26 DLBCL patients and 13 age-matched healthy controls (HC) were analysed. The cytotoxic CD56

Introduction: Acute undifferentiated leukemia (AUL), also referred to as ambiguous lineage leukemia, has been recognized as a unique entity by the WHO classification of myeloid neoplasms since 2008, and is considered a rare subtype. It is characterized by lacking expression of markers diagnostic of myeloid or lymphoid lineages, and encompasses the provisional entity of myeloid/natural killer (NK) leukemia, which also expresses CD56 and other immature T-cell markers. Small studies have reported that AUL is associated with a poor prognosis; however, cytogenetic and molecular characterization of this subgroup of patients is lacking, as are the long-term outcomes of induction therapy and stem cell transplantation (SCT). The goal of this study was to assess clinical and laboratory data of patients diagnosed with AUL at our institution, focusing on its unique characteristics and response to initial therapy. Methods: Parameters assessed at diagnosis included: initial blood counts, bone marrow (BM) blast cell percentage by morphology, specific phenotypic characteristics of BM blasts, molecular mutations and translocations, as well as cytogenetic abnormalities. Immunophenotyping of BM cells at diagnosis was performed using eight-color flow cytometry. Multi-parameter Cytognos acute orientation tube (ALOT) and the combination of the following antigens were used: CD34/CD117/CD14/CD56/CD36/CD123/HLA-DR/CD45/CD64/CD11c. Data were acquired with FACSCanto II flow cytometer and analyzed with Infinicyt software. Myeloperoxidase staining by fluorescence-activated cell sorting (FACS) was considered negative if Results: One hundred and sixteen cases of acute myeloid leukemia were diagnosed at the Rambam Health Care Campus between 11/2016 and 5/2018; 16 (1.4%) of them were defined as AUL, since they did not qualify for myeloid, B- or T-cell lineage according to the WHO classification. CD56 positivity was demonstrated in 8 (50%) cases, 5 of which were also CD7 positive. Patient median age was 63 years, 56% were men. None of the patients was found positive for either NPM1 or FLT3 mutations. Likewise, no core binding leukemias were diagnosed in this cohort. Sixty six percent (10/15) of the BM samples demonstrated cytogenetic and/or FISH abnormalities, with 26% complex karyotype cases, and 20% chromosome 7 aberrancies. All but two patients were treated with AML-oriented therapies. None of the patients achieved remission with induction therapy regardless of whether it included a chemotherapy backbone (82% of patients) or a hypomethylating agent. Seven patients have undergone allogeneic SCT, 4 of whom are in remission to date. Two of the remaining transplanted patients died of progressive disease and one developed extramedullary relapse 6 months post-transplant. While 8/16 (50%) patients are alive at 18-month follow-up, only 4 of them (25%) are in remission. Notably, all of the latter patients are SCT recipients. Six out of 8 CD56-positive patients have died of progressive disease, and the remaining two have not achieved remission. Conclusions: The present study, while confirming the poor prognosis of AUL patients, also suggests that a certain subset of such individuals could benefit from an allogeneic SCT. The high percentage of complex karyotype abnormalities, the lack of NPM1 mutations, and the expression of T/NK cell immaturity markers could partly account for the established poor outcome. However, since other molecular abnormalities described in the AML mutational landscape may be involved in AUL initiation/progression, extensive molecular sequencing of this patient population is required. A better understanding of the unique characteristics of this leukemia subtype is also crucial for the design of potentially improved treatment strategies for AUL patients. Disclosures No relevant conflicts of interest to declare.