Germline mutations in the MEN1 gene encoding menin protein cause multiple endocrine neoplasia type 1 (MEN1) syndrome. Recent evidence suggests that inhibiting the interaction of menin with its crucial oncogenic protein partners represents a promising therapeutic strategy to AML. Menin plays a critical role in lysine methyltransferase 2A (KMT2A)-gene-rearranged and NPM1-m acute leukemias, both associated with adverse outcomes with current standard therapies, especially in the relapsed/refractory setting. Disrupting the menin–KMT2A interaction affects the proleukemogenic HOX/MEIS transcription program. This disruption leads to the differentiation of KMT2Ar and NPM1-m AML cells. Small molecular inhibitors of the menin–KMT2A interaction target the central cavity of MEN1 to inhibit the MEN1-KMT2A interaction and could target a similar transcriptional dependency in other leukemia subsets, broadening their therapeutic potential. These agents, both as monotherapies and in combination with synergistic drugs, are undergoing preclinical and clinical evaluation with promising early results. With the growing literature around menin inhibitors in AML, we discussed the biology of menin, its mechanism of action, its interacting partners in leukemia, possible inhibitors, their implications, synergistic drugs, and future therapeutic strategies in this review.

Background: While NPM1-mutated AML in the absence of FLT3-ITD generally carries a favorable prognosis, large registry studies suggest the positive prognostic benefit may not extend to patients > 65 years of age. We examined this preferential, age-dependent prognostic impact through a real-world analysis of 2811 adult AML patients. Results: The median overall survival (OS) was significantly better in NPM1^MT compared to NPM1^WT patients [20.86 vs. 17 mo., p = 0.003]. When stratified by age, NPM1^MT patients had higher OS than NPM1^WT patients in the 55–65-year age group (28.62 vs. 16.3 mo., p ≤ 0.0001). This OS benefit was heterogenous and prevailed most strikingly in the 55–60 (68.3 vs. 15.6 mo., p = 0.002), and up to the 60–65-year group (mOS not estimable vs. 20 mo., p = 0.007), but not beyond 65 y. Notably, the ≤65 cohort was more enriched with dominant NPM1 (21% vs. 15%, p ≤ 0.001), while the >65 cohort was enriched with abnormal karyotype (20% in >65 years vs. 16% in ≤65 years, p = 0.001), and co-occurring SRSF2 and ASXL1 mutations (18.7% vs. 7.5%, p ≤ 0.0001 and 13.5% vs. 4.1%, p ≤ 0.0001 resp.). Conclusions: We demonstrate that in a real-world setting, the prognostic benefit of NPM1 does not extend beyond age 65, underscoring the need for age-adapted risk stratification models. This granular approach could prevent the potential overestimation of prognosis in older patients with NPM1^MT AML and inform therapeutic decision making.

With more than 54 million cases worldwide, the novel coronavirus disease 2019 (COVID-19) has disrupted every aspect of public life and poses an ever-growing burden on an already strained healthcare system. The emergence of new COVID-19 hot-spots and super-spreader events are placing an immense amount of stress on hospital systems responding to the increased influx of critically ill patients. Healthcare workers and frontline physicians disproportionately bear the additional physical and psychological burdens associated with the appearance of a new hot-spot. However, the mental health implications of COVID-19 for physicians are not well understood. In this perspective piece, we discuss widespread effects of the ongoing pandemic on physician mental health and how blockchain infrastructure can enable digital health technologies in supporting data-driven fatigue mitigation interventions. This is particularly applicable to simplifying physician workflows in newly emerging hot-spots.

We report two cases of pancytopenia in patients after recovering from a mild COVID-19, now presenting as paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. These cases illustrate a common pathway whereby a viral trigger causes the clonal expansion of a hematological disorder. Although the association of both cases with COVID-19 is temporal and COVID-19 may be an incidental diagnosis, the growing evidence related to the hematological effects of SARS-CoV-2 infection highlights the need for further investigation into the hematological consequences of COVID-19, particularly in the post-pandemic era.

We report two cases of pancytopenia in patients after recovering from a mild COVID-19, now presenting as paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. These cases il-lustrate a common pathway whereby a viral trigger causes clonal expansion of a hematological disorder. Although the association in both cases are temporal, and that COVID-19 may be an in-cidental diagnosis, the growing evidence related to hematological effects of SARS-CoV-2 infec-tion highlights the need for further investigation into the hematological consequences of COVID-19, particularly in the post-pandemic era.