Long non-coding RNAs (lncRNAs) represent the majority of cellular transcripts and play pivotal roles in hematopoiesis. However, their clinical relevance in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) remains largely unknown. Here, we investigated the functions of HOXB-AS3, a lncRNA located at human HOXB cluster, in the myeloid cells, and analyzed the prognostic significances in patients with AML and MDS. shRNAs were used to downregulate HOXB-AS3 in the cell lines and the effect was evaluated by quantitative polymerase chain reaction. The proliferation of the cell lines was illustrated by proliferation and BrdU flow assays. Further, we retrospectively analyzed the HOXB-AS3 expression in 193 patients with AML and 157 with MDS by microarray analysis, and evaluated its clinical importance. Downregulation of HOXB-AS3 suppressed cell proliferation. Mechanistically, HOXB-AS3 potentiated the expressions of several key factors in cell cycle progression and DNA replication without affecting the expressions of HOX genes. In AML, patients with higher HOXB-AS3 expression had shorter survival than those with lower HOXB-AS3 expression (median overall survival (OS), 17.7 months versus not reached, P < 0.0001; median relapse-free survival, 12.9 months versus not reached, P = 0.0070). In MDS, patients with higher HOXB-AS3 expression also had adverse prognosis compared with those with lower HOXB-AS3 expression (median OS, 14.6 months versus 42.4 months, P = 0.0018). The prognostic significance of HOXB-AS3 expression was validated in the TCGA AML cohort and another MDS cohort from our institute. The subgroup analyses in MDS patients showed that higher HOXB-AS3 expressions could predict poor prognosis only in lower-risk (median OS, 29.2 months versus 77.3 months, P = 0.0194), but not higher-risk group. This study uncovers a promoting role of HOXB-AS3 in myeloid malignancies and identifies the prognostic value of HOXB-AS3 expression in AML and MDS patients, particularly in the lower-risk group.

Acute myeloid leukaemia (AML) with central nervous system (CNS) involvement in adults is uncommon, and studies of this subject are scant. We conducted a retrospective study to investigate the clinical aspects, cytogenetic abnormalities, molecular gene mutations and outcomes of adult AML patients with CNS involvement. Three hundred and ninety-five patients with newly diagnosed AML were reviewed. Twenty (5.1%) patients had CNS involvement, including 7 (1.8%) with initial CNS disease and 4 (1%) who suffered an isolated CNS relapse. The patients with CNS involvement were younger, had higher leukocyte, platelet, and peripheral blast cell counts, FAB M4 morphology, and chromosome translocations involving 11q23 (11q23 abnormalities) more frequently than did the patients without CNS involvement. No differences in sex, haemoglobin levels, serum LDH levels, immunophenotype of leukaemia cells, or molecular gene mutations were observed between the two groups. Multivariate analyses showed that age ≤ 45 years (OR, 5.933; 95% CI, 1.82 to 19.343), leukocyte counts ≥ 50,000/μl (OR, 3.136; 95% CI, 1.083 to 9.078), and the presence of 11q23 abnormalities (OR, 5.548; 95% CI, 1.208 to 25.489) were significant predictors of CNS involvement. Patients with initial CNS disease had 5-year overall survival and relapse-free survival rates that were similar to those without initial CNS disease. However, three of four patients who suffered an isolated CNS relapse died, and their prognosis was as poor as that of patients who suffered a bone marrow relapse. CNS involvement in adult patients with AML is rare. Three significant risk factors for CNS involvement including age ≤ 45 years, leukocyte counts ≥ 50,000/μl and the presence of 11q23 abnormalities were identified in this study. Future investigations to determine whether adult AML patients having these specific risk factors would benefit from CNS prophylactic therapy are necessary.

DNMT3A gene mutation has been associated with poor prognosis in acute myeloid leukemia, but its clinical implications in myelodysplastic syndrome (MDS) and dynamic changes during disease progression remain controversial. In this study, DNMT3A mutation was identified in 7.9% of 469 de novo MDS patients. DNMT3A-mutated patients had higher platelet counts at diagnosis, and patients with ring sideroblasts had the highest incidence of DNMT3A mutations, whereas those with multilineage dysplasia had the lowest incidence. Thirty-one (83.8%) of 37 DNMT3A-mutated patients had additional molecular abnormalities at diagnosis, and DNMT3A mutation was highly associated with mutations of IDH2 and SF3B1. Patients with DNMT3A mutations had a higher risk of leukemia transformation and shorter overall survival. Further, DNMT3A mutation was an independent poor prognostic factor irrespective of age, IPSS-R, and genetic alterations. The sequential study demonstrated that the original DNMT3A mutations were retained during follow-ups unless allogeneic hematopoietic stem cell transplantation was performed, while DNMT3A mutation was rarely acquired during disease progression. DNMT3A mutation predicts unfavorable outcomes in MDS and was stable during disease evolutions. It may thus be a potential biomarker to predict prognosis and monitor the treatment response.

This study investigated the correlation of body mass index (BMI) and proinflammatory cytokine levels with hematopoietic stem cell (HSC) mobilization triggered by granulocyte colony-stimulating factor (G-CSF). Stem cell donors (n = 309) were recruited between August 2015 and January 2018 and grouped into four groups according to their BMI: underweight (BMI < 18.5 kg/m², n = 10), normal (18.5 kg/m² ≦ BMI < 25 kg/m², n = 156), overweight (25 kg/m² ≦ BMI < 30 kg/m², n = 102), and obese (BMI ≧ 30 kg/m², n = 41). The participants were then administered with five doses of G-CSF and categorized as good mobilizers (CD34 ≧ 180/μL, n = 15, 4.85%) and poor mobilizers (CD34 ≦ 25/μL, n = 14, 4.53%) according to the number of CD34⁺ cells in their peripheral blood after G-CSF administration. The correlation between BMI and HSC mobilization was then analyzed, and the levels of proinflammatory cytokines in the plasma from good and poor mobilizers were examined by ProcartaPlex Immunoassay. Results showed that BMI was highly correlated with G-CSF-triggered HSC mobilization (R² = 0.056, p < 0.0001). Compared with poor mobilizers, good mobilizers exhibited higher BMI (p < 0.001) and proinflammatory cytokine [interferon gamma (IFN-γ) (p < 0.05), interleukin-22 (IL-22) (p < 0.05), and tumor necrosis factor alpha (TNF-α) levels (p < 0.05)]. This study indicated that BMI and proinflammatory cytokine levels are positively correlated with G-CSF-triggered HSC mobilization.

Background: The two most noteworthy strategies for haploidentical stem cell transplantation (haplo-HSCT) are posttransplantation cyclophosphamide (PTCy) with or without thymoglobulin (ATG) and granulocyte colony stimulating factor-primed bone marrow plus peripheral blood stem cells (GIAC). We aimed to compare these approaches in patients with hematological malignancies. Methods: We enrolled 178 patients undergoing haplo-HSCT, including modified GIAC (mGIAC), PTCy without ATG, and PTCy with ATG. Results: The patients in the mGIAC group had the most favorable platelet and neutrophil engraftment kinetics. Although the grade III–IV acute graft-versus-host-disease (GvHD) rates were similar, those receiving mGIAC had a significantly higher extensive chronic GvHD rate. The patients receiving mGIAC had a similar cumulative incidence of relapse (CIR) to that in the patients receiving PTCy with ATG, but this was lower than that in the patients receiving PTCy without ATG. The patients receiving mGIAC had the lowest nonrelapse mortality (NRM) and the highest overall survival (OS) rates. The differences in CIR, NRM, and OS remained significant when focusing on patients with low/intermediate-risk diseases before haplo-HSCT. Intriguingly, among patients with high/very-high-risk diseases before haplo-HSCT, no differences were observed in the CIR, NRM, OS, or GvHD/relapse-free survival. Conclusion: the mGIAC approach may yield a better outcome in Taiwanese patients with hematologic malignancies, especially for those with low/intermediate-risk diseases.

Psychological stress is widely acknowledged as a major contributor to immunosuppression, rendering individuals more susceptible to various diseases. The complex interplay between the nervous, endocrine, and immune systems underlies stress-induced immunosuppression. However, the underlying mechanisms of psychological-stress-induced immunosuppression remain unclear. In this study, we utilized a restraint stress mouse model known for its suitability in investigating physiological regulations during psychological stress. Comparing it with cold exposure, we observed markedly elevated levels of stress hormones corticosterone and cortisol in the plasma of mice subjected to restraint stress. Furthermore, restraint-stress-induced immunosuppression differed from the intravenous immunoglobulin-like immunosuppression observed in cold exposure, with restraint stress leading to increased macrophage cell death in the spleen. Suppression of pyroptosis through treatments of inflammasome inhibitors markedly ameliorated restraint-stress-induced spleen infiltration and pyroptosis cell death of macrophages in mice. These findings suggest that the macrophage pyroptosis associated with restraint stress may contribute to its immunosuppressive effects. These insights have implications for the development of treatments targeting stress-induced immunosuppression, emphasizing the need for further investigation into the underlying mechanisms.