Background Decitabine is widely used in China for high-risk myelodysplastic syndromes (MDS). However, the prognostic factors associated with overall survival (OS) remain incompletely defined. Methods We retrospectively analyzed 130 high-risk MDS patients treated with decitabine. Clinical characteristics and laboratory parameters were collected. Treatment response was assessed, and survival outcomes were evaluated using Cox regression models. A prognostic nomogram was developed to improve risk stratification beyond the conventional IPSS/IPSS-R systems. Results The median age was 60.5 years, with 57.7% male patients. Median OS was 15.5 months. Univariate analysis showed that age ≥50 years, bone marrow blasts ≥10%, and iron overload (serum ferritin ≥500 µg/L) were significantly associated with inferior OS. Multivariate Cox regression confirmed age ≥50 (HR = 2.31, 95% CI: 1.21–4.40, p = 0.011) and elevated bone marrow blasts (HR = 1.92, 95% CI: 1.16–3.17, p = 0.012) as independent adverse prognostic factors. Poor karyotype also conferred poor outcomes. Next-generation sequencing data were available for 92 patients. Given the low mutation rate, the mutational analysis was conducted exploratorily; results suggested that TP53 mutations were significantly associated with adverse prognosis. A prognostic nomogram integrating age, ECOG score, bone marrow blasts, cytogenetics, hemoglobin, platelet count, absolute neutrophil count, ring sideroblasts, and ferritin demonstrated improved risk stratification, though validation was limited to internal cohorts. Conclusion Decitabine provides short-term hematologic benefits in high-risk MDS, but overall prognosis remains poor. Age, bone marrow blasts, iron overload, and high-risk cytogenetics are key prognostic factors. Incorporating clinical, cytogenetic, and mutational variables into new prognostic models may enhance individualized treatment decision-making for high-risk MDS patients.

ABSTRACT Background and Objectives: Blood transfusion is a vital medical procedure, yet it carries the risk of transmitting infectious diseases. This study aimed to assess the demographic characteristics and transfusion-transmitted infection (TTI) profiles of family replacement and voluntary blood donors in Saudi Arabia. Materials and Methods: A retrospective cross-sectional analysis was conducted using records from 49,590 blood donors at King Fahad Medical City, Riyadh, Saudi Arabia. Donors were classified as family replacement or voluntary. Demographic information and results of screening for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), syphilis, and malaria were analysed. Statistical analyses included descriptive statistics, chi-square testing, stratified analysis by nationality, and logistic regression. Results: 49,590 donors were included, 10.6% were family replacement and 89.4% were voluntary. Males accounted for 92.6% of the donor population. No significant differences were observed between the two groups for HBV, HCV, HIV, or syphilis. However, malaria prevalence was significantly higher among family replacement donors (5.3%) compared to voluntary donors (2.9%). Family replacement donation was more common among younger donors, males, and non-Saudi nationals.‏ The higher malaria prevalence among family replacement donors was particularly evident among non-Saudi donors, and regression analysis confirmed that nationality modified the association between donation type and malaria positivity. Conclusion: While rates of major viral TTIs were comparable between donor types, malaria risk was significantly higher among family replacement donors, especially among non-Saudi donors. These findings highlight the importance of continued malaria screening and donor selection strategies to maintain safe blood transfusion practices in Saudi Arabia.

ABSTRACT Objectives Langerhans Cell Histiocytosis (LCH) is an inflammatory myeloid neoplasm with heterogeneous outcomes. This study aimed to identify independent risk factors influencing event-free survival (EFS) in pediatric LCH, focusing on initial white blood cell (WBC) counts and disease extent. Methods We retrospectively analyzed 67 pediatric LCH patients with bone involvement treated at Hebei Children's Hospital, Hebei Clinical Medicine Research Center for Children's Health and Diseases between 2013 and 2022. The primary endpoint was EFS. Cox proportional hazards regression models determined predictors of adverse outcomes. Results The 3-year EFS rate was 76.1% (median follow-up: 48 months). Univariate analysis linked multiple disease sites, risk-organ involvement, CNS risk site involvement, diabetes insipidus, and elevated WBC count to poor EFS. In multivariate analysis, only multiple site involvement (Hazard Ratio [HR] = 3.12, p = 0.025) and an elevated initial WBC count (>10 × 10⁹/L) (HR = 2.89, p = 0.034) remained independent predictors. Discussion While risk-organ involvement is a traditional stratifier, systemic inflammatory burden, reflected by leukocytosis, offers independent prognostic value. Patients with elevated WBC counts or multisite disease warrant intensive monitoring. Conclusion Elevated initial WBC count and multiple site involvement independently predict shorter EFS in pediatric LCH. Integrating these markers into risk stratification could optimize therapies.

ABSTRACT Objective TMEM91::TAL1 fusion has been identified in glioblastoma but has never been documented in hematologic malignancies. We document the first presentation of the TMEM91::TAL1 fusion in a myelodysplastic syndrome (MDS) with rapid transition into secondary acute myeloid leukemia (sAML). Case presentation A middle-aged female presented to the hematology clinic complaining primarily of fatigue and a workup revealing pancytopenia. Bone marrow (BM) biopsy demonstrated 8% blasts with myelodysplastic changes and secondary myelofibrosis. RNA sequencing detected the TMEM91::TAL1 fusion at 1.79% in the presence of normal cytogenetics and a minimal inhibitory DNMT3A mutation (1.3%). Despite multiple cycles of azacitidine, within one month, the patient had transitioned into sAML with blasts increased to 55% with heterogeneity in the sample, and TMEM91::TAL1 expression increased to 2.83%. The patient underwent haploidentical stem cell transplantation with complete remission and no evidence of TMEM91::TAL1 fusion. Discussion: and conclusions The TMEM91::TAL1 fusion (resulting from a breakpoint at exon 3 of TMEM91 and exon 5 of TAL1) was detected by RNA-seq while not detected by whole genome sequencing. The expression of TMEM91::TAL1 fusion increased with the progression from MDS to sAML and was eliminated after HSCT. This case illustrates the value of comprehensive molecular profiling, including RNA-seq, in cases of rapidly progressive MDS that cannot be diagnosed through standard molecular diagnostics. The temporal relationship between expression of the fusions and disease progression warrants additional studies of TMEM91::TAL1 in myeloid malignancies.

ABSTRACT Objective To investigate the effects of the PI3 K inhibitor, linperlisib (YY20394), on proliferation, apoptosis, cell cycle and signaling pathways in acute myeloid leukemia (AML) cells. Methods The U937 cell cultures were treated with different concentrations of YY20394 to determine the IC50 value by analyzing the cell viability using Cell Counting Kit-8(CCK8). The obtained IC50 value was used for selecting the appropriate concentrations for studies on apoptosis and cell cycle changes using AO/EB dual fluorescence staining and flow cytometry respectively. The effects of YY20394 on signaling pathways at different concentrations were detected by real-time quantitative PCR (RT–PCR) and Western blotting. Results Compared with the control group, YY20394 significantly increased the inhibition rate of proliferation and the apoptosis rate of AML cells (P < 0.05). Treatment with 5 μM YY20394 led to cell cycle arrest predominantly in the G1phase, while 10um treatment resulted in cell cycle arrest mainly in the G2 phase. Interestingly, YY20394 did not exert its anti-leukemic effects through modulation of the PI3 K/Akt/mTOR Signaling pathway, suggesting that alternative molecular mechanisms may be involved. Conclusion YY20394 has a favorable inhibitory effect and significant pro-apoptotic effect on the proliferation of AML cells, which suggests that it has some potential for the treatment of AML.

ABSTRACT Background Autologous hematopoietic stem cell transplantation (auto-HSCT) is standard for eligible multiple myeloma (MM) patients, yet outcomes are heterogeneous. Besides established markers like cytogenetics and ISS, the independent prognostic value of pretreatment hemoglobin (Hb), myeloma subtype, and induction regimen requires clarification. This study aimed to assess these factors to improve risk stratification. Methods We retrospectively analyzed 350 MM patients undergoing first auto-HSCT at Beijing Chao-Yang Hospital (2001–2019). The impact of baseline Hb (<10 vs. ≥10 g/dL), subtype (IgG vs. non-IgG), and induction regimen (bortezomib-based vs. others) on progression-free survival (PFS) and overall survival (OS) was evaluated using Kaplan-Meier and Cox regression. Results With a median follow-up of 58 months, median PFS and OS were 42 months (95% CI 36–48) and 98 months (95% CI 83–113), respectively. Multivariate analysis identified three independent predictors of superior PFS: Hb ≥10 g/dL (HR = 0.65, P = 0.012), IgG subtype (HR = 0.72, P = 0.018), and bortezomib-based induction (HR = 0.58, P = 0.004). Attaining CR/VGPR post-transplant also significantly prolonged PFS versus PR or less (median 55 vs. 37 months, P = 0.044). Conclusion Pretreatment hemoglobin, IgG subtype, and bortezomib-based induction are independent predictors of survival after auto-HSCT. Hb, a simple and widely available marker, adds prognostic value beyond ISS and cytogenetics. Integrating these factors into prognostic models can help tailor therapy and improve patient management.

ABSTRACT Objectives: Chromosome 7 abnormality characterized by loss of both arms [der(7)del(7p)del(7q), hereafter ‘der(7)’] is very rare. The features and prognosis of patients with der(7) in myelodysplastic syndromes (MDS) remain unclear. Methods: We identified 35 MDS cases with der(7) using Metaphase Fluorescence In Situ Hybridization (metaphase-FISH), and compared them to 178 with del(7q), 390 with monosomy 7 (−7), and 603 with a normal karyotype (NK). Results: Der(7) correlated with lower karyotypic complexity (odds ratios (ORs) 0.288, P = 0.001), more solitary abnormalities (ORs 3.652, P = 0.001), and frequent co-occurrence with −7 (40.9%; ORs 3.150, P = 0.004). Compared to NK, der(7) cases presented lower platelet counts, higher ferritin levels, and more frequent ≥3 mutations (P < 0.05). Mutations in ASXL1(ORs 2.394), RUNX1(ORs 2.618), SETBP1(ORs 15.132), and ETV6 (ORs 5.525) were enriched in der(7)/−7/del(7q) patients compared to NK (all P < 0.001), while NF1 (ORs 15.492, P = 0.002) and PTPN11 (ORs 6.653, P = 0.021) mutations were more prevalent in der(7) cases relative to NK. Prognostically, der(7) was identified as an independent risk factor (Hazard Ratios (HRs) 1.368, 95% CI 1.030–1.818; P = 0.031). Median overall survival (OS) of patients with der(7) was 17 months – shorter than NK (64 months, P = 0.005) but similar to −7 (20 months) and del(7q) (30 months). Hematopoietic stem cell transplantation improved survival (P = 0.018). Notably, 5 of 10 der(7) cases with follow-up evolved to −7. Conclusion: Der(7) defines a distinct high-risk subgroup with a unique molecular profile and poor prognosis comparable to −7.

ABSTRACT Background Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count (PLT). Bruton tyrosine kinase (BTK) is a therapeutic target in immune-mediated diseases. This study aimed to evaluate the effects of a BTK inhibitor, zanubrutinib (Zan), on refractory ITP. Methods Peripheral blood was collected from healthy controls (HC) and refractory ITP patients (n = 15), and peripheral blood mononuclear cell (PBMC) extraction was performed. The proportion of myeloid-derived suppressor cells (MDSCs) in PBMCs and Arg-1, iNOS, Fc gamma receptor (FcγR), GPIIb/IIIa, and GPIb/IX autoantibody levels were measured. ITP monocytes were separated into control (Con), Zan (Zan), dexamethasone (DXM), and combination (Zan + DXM) groups. Detection ophagocytosis and platelet activation by flow cytometry; FcγR expression by qRT-PCR and western blot; and IFN-γ, IL-4, IL-2, and IL-10 levels were determined by ELISA. Results PBMCs from the ITP group demonstrated lower MDSCs proportions and Arg-1 levels, but higher iNOS, FcγRIII, FcγRIIb, FcγRI, GPIIb/IIIa, and GPIb/IX autoantibody levels than those in the HC group. Following Zan intervention, ITP monocytes exhibited decreased phagocytosis, FcγRIIa, FcγRI protein, IFN-γ, IL-2, p-mTOR/mTOR levels, and increased FcγRIIb, PLTs, IL-4, PAC-1, and CD62p levels. Conclusion Zan may modulate FcγR toward FcγRIIb to inhibit platelet destruction, thereby improving refractory ITP.

ABSTRACT Introduction: Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by thrombocytopenia in the absence of another cause. Our aim is to analyze mortality trends related to ITP in the United States (US) population from 1999 to 2022. Methods: We extracted age-adjusted mortality rates (AAMR) per 100,000 population for ITP-related deaths in the United States from 1999 to 2022 using the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database from 1999 to 2022. AAMRs were stratified by year, gender, race or ethnicity, and geographical distribution. Joinpoint regression was used to calculate annual percent change (APC) and average annual percent change (AAPC) through the Joinpoint Regression Program (V 5.1.0, National Cancer Institute). Results: From 1999 to 2022, a total of 17,069 ITP-related deaths occurred in the US. Males exhibited a higher overall AAMR (0.22) in comparison to females (0.17). NH Whites exhibited the highest overall AAMR (0.20). Stratification by geographical location revealed non-metropolitan areas to have a higher overall AAMR (0.24) than metropolitan areas (0.19). The Midwest exhibited the highest overall AAMR (0.22). Vermont (0.37), Rhode Island (0.35), and North Dakota (0.32) were among the states with the highest overall AAMR, whereas states on the other end of the spectrum included Nevada (0.13), the District of Columbia (0.14) and Louisiana (0.15). Conclusion: The disparities identified in our analysis, particularly among NH Whites, the elderly, and residents of the Midwest and rural areas, suggest underlying healthcare access issues, potential genetic predispositions, and regional differences in treatment strategies.

ABSTRACT Background: Multiple myeloma (MM) is a malignant plasma-cell disease. Epigenetic modifications, including acetylation, are thought to contribute to tumorigenesis. N-acetyltransferase 10 (NAT10) is an important regulator of mRNA acetylation in various tumors. In this study, we explored the functions and mechanisms of action of NAT10 in MM. Methods: The expression of G protein-coupled receptor 37 (GPR37) and NAT10 was determined by qRT-PCR and western blotting, respectively. Cell proliferation was assessed using MTT and EdU assays. Cell apoptosis and cell cycle processes were analyzed using flow cytometry. Glycolysis levels were estimated using relevant commercial kits. The relationship between GPR37 and NAT10 was analyzed using the Acetylated RNA immunoprecipitation (acRIP), RIP and Actinomycin D assays. A murine xenograft model was constructed to explore the functional roles of GPR37 and NAT10 in tumor growth in vivo. Results: GPR37 was highly expressed in MM sera and cells. GPR37 knockdown inhibited MM cell proliferation, cell cycle, glycolysis, and immune escape and facilitated apoptosis in vitro. Mechanistically, NAT10 positively modulated GPR37 expression through the ac4C modification of GPR37 mRNA. Moreover, our results showed that NAT10 knockdown repressed MM cell proliferation, cell cycle, glycolysis, and immune escape; facilitated apoptosis in vitro and inhibited tumor growth in vivo by regulating GPR37 expression. Conclusion: NAT10 aggravated MM malignancy by regulating GPR37 expression. These results indicate that NAT10 and GPR37 may be novel targets for MM therapy.