Aplastic anemia (AA) is an auto-activated T cell–mediated bone marrow failure. Cyclosporine is often used to treat non-severe AA, which demonstrates a more heterogeneous condition than severe AA. The response rate to cyclosporine is only around 50% in non-severe AA. To better predict response to cyclosporine and pinpoint who is the appropriate candidate for cyclosporine, we performed phenotypic and functional T cell immune signature at single cell level by mass cytometry from 30 patients with non-severe AA. Unexpectedly, non-significant differences of T cell subsets were observed between AA and healthy control or cyclosporine-responder and non-responders. Interestingly, when screening the expression of co-inhibitory molecules, T cell trafficking mediators, and cytokines, we found an increase of cytotoxic T lymphocyte antigen 4 (CTLA-4) on T cells in response to cyclosporine and a lower level of CTLA-4 on CD8 + T cells was correlated to hematologic response. Moreover, a decreased expression of sphingosine-1-phosphate receptor 1 (S1P 1 ) on naive T cells and a lower level of interleukin-9 (IL-9) on T helpers also predicted a better response to cyclosporine, respectively. Therefore, the T cell immune signature, especially in CTAL-4, S1P 1 , and IL-9, has a predictive value for response to cyclosporine. Collectively, our study implies that immune signature analysis of T cell by mass cytometry is a useful tool to make a strategic decision on cyclosporine treatment of AA. Supplementary information The online version contains supplementary material available at 10.1007/s00277-023-05097-6.

To the Editor, Aplastic anemia (AA) is an auto-activated T cell-mediated bone marrow failure, characterized by pancytopenia and hypocellular marrow. 1 With the worldwide spread of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, patients with AA are at high risk for infection due to disease-related neutropenia and enduring immunosuppressive therapy (IST). 2 Furthermore, AA patients often do not receive the SARS-CoV-2 vaccination due to an ineffective protective specific antibody response to viral antigens and potential immune system activation that may worsen underlying marrow failure.Prior studies have evaluated the clinical manifestation of SARS-CoV-2 infection in severe or very severe AA (SAA/VSAA) patients through case reports or case series, 3-8 but the severity and long-term prognosis of SARS-CoV-2 infection in AA is still not clear.To better explore whether patients with AA experienced more severe symptoms of infection or demonstrated higher relapse rate after infection, we prospectively collected 175 AA patients enrolled in National Longitudinal Cohort of Hematological Diseases (NICHE, NCT04645199) and described the clinical features and outcomes of AA after infecting Omicron SARS-CoV-2 between December 2022 and January 2023. This study demonstrated a low risk of relapse in AA after Omicron infection.In this study, SARS-CoV-2 illness severity was evaluated by the National Institutes of Health COVID-19 Treatment Guidelines. Severe illness was defined as individuals who had SpO 2 < 94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen <300 mmHg, a respiratory rate > 30 breaths/min, or lung infiltrates >50%. Hematological responses were evaluated based on established criteria. 9 Robust response was defined as not only meeting standard response criteria, 9 but fulfilling more than 50 Â 10 9 /L of platelet and 100 g/L of hemoglobin (Hb). A progressive and substantial decline in blood counts requiring reinitiation of highdose cyclosporine or androgen or thrombopoietin receptor agonists was defined as relapse. Paired t-tests were used to compare the hematological indices before and after Omicron infection, including Hb, platelet, neutrophil, and lymphocyte counts.The study engaged a total of 175 patients, comprising 90 males and 85 females, with a median age of 33 years (range, 10-72). Among these patients, 29.7% had SAA/VSAA, 14.3% had transfusiondependent AA, and 56.0% had transfusion-independent AA. Forty-six

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy with dismal prognosis. Identification of better biomarkers remained a priority to improve established stratification and guide therapeutic decisions. Therefore, we extracted the RNA sequence data and clinical characteristics of AML from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression database (GTEx) to identify the key factors for prognosis. We found UNC93B1 was highly expressed in AML patients and significantly linked to poor clinical features (p &lt; 0.05). We further validated the high expression of UNC93B1 in another independent AML cohort from GEO datasets (p &lt; 0.001) and performed quantitative PCR of patient samples to confirm the overexpression of UNC93B1 in AML (p &lt; 0.005). Moreover, we discovered high level of UNC93B1 was an independent prognostic factor for poorer outcome both in univariate analysis and multivariate regression (p &lt; 0.001). Then we built a nomogram model based on UNC93B1 expression, age, FAB subtype and cytogenetic risk, the concordance index of which for predicting overall survival was 0.729 (p &lt; 0.001). Time-dependent ROC analysis for predicting survival outcome at different time points by UNC93B1 showed the cumulative 2-year survival rate was 43.7%, and 5-year survival rate was 21.9%. The differentially expressed genes (DEGs) between two groups divided by UNC93B1 expression level were enriched in innate immune signaling and metabolic process pathway. Protein–protein interaction (PPI) network indicated four hub genes (S100A9, CCR1, MRC1 and CD1C) interacted with UNC93B1, three of which were also significantly linked to inferior outcome. Furthermore, we discovered high UNC93B1 tended to be infiltrated by innate immune cells, including Macrophages, Dendritic cells, Neutrophils, Eosinophils, and NK CD56dim cells. We also found UNC93B1 had a significantly positive correlation with CD14, CD68 and almost all Toll-like receptors. Finally, we revealed negatively correlated expression of UNC93B1 and BCL2 in AML and conjectured that high-UNC93B1 monocytic AML is more resistant to venetoclax. And we found high MCL-1 expression compensated for BCL-2 loss, thus, we proposed MCL-1 inhibitor might overcome the resistance of venetoclax in AML. Altogether, our findings demonstrated the utility of UNC93B1 as a powerful poor prognostic predictor and alternative therapeutic target.