Blood ResearchPub Date : 2026-03-06DOI: 10.1007/s44313-026-00126-5
Kyoung Il Min, Gi-June Min, Ki-Seong Eom, Seok-Goo Cho
{"title":"Rapidly progressive varicella zoster virus vasculopathy in a chemotherapy- and steroid-immunosuppressed patient with refractory diffuse large B-cell lymphoma: diagnostic and therapeutic challenges.","authors":"Kyoung Il Min, Gi-June Min, Ki-Seong Eom, Seok-Goo Cho","doi":"10.1007/s44313-026-00126-5","DOIUrl":"10.1007/s44313-026-00126-5","url":null,"abstract":"<p><p>Varicella zoster virus (VZV) vasculopathy is a rare but severe neurological complication that frequently results in a reversible cerebral vasoconstriction syndrome (RCVS). Diagnosis is often delayed because early manifestations are nonspecific and radiologic findings often overlap with those of other cerebrovascular disorders. We describe the fatal case of a heavily pretreated 60-year-old man with refractory diffuse large B-cell lymphoma undergoing evaluation for chimeric antigen receptor (CAR) T-cell therapy. The patient developed multifocal intracranial arterial stenosis and an acute infarction during chemotherapy-induced immunosuppression. The initial radiological features suggested RCVS; however, cerebrospinal fluid (CSF) analysis using polymerase chain reaction (PCR) and anti-IgG antibodies confirmed the presence of VZV. Despite intravenous acyclovir and high-dose corticosteroids, the vasculopathy progressed rapidly, resulting in recurrent infarctions, seizures, and death. This case highlights the diagnostic complexity of VZV vasculopathy in immunocompromised patients and underscores the importance of early CSF evaluation, heightened clinical vigilance for opportunistic viral complications, and the potential diagnostic value of vessel wall magnetic resonance imaging (MRI) in differentiating VZV vasculopathy from mimicking conditions such as RCVS.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12965949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Discordance between immunofixation and free light chain assays in multiple myeloma: a retrospective analysis and evaluation of the heavy/light chain assay for disease monitoring.","authors":"Oytip Nathalang, Yupapin Onthong, Chonlada Laoruangroj, Dollapak Apipongrat","doi":"10.1007/s44313-026-00130-9","DOIUrl":"10.1007/s44313-026-00130-9","url":null,"abstract":"<p><strong>Background: </strong>Accurate detection and monitoring of monoclonal proteins in multiple myeloma (MM) are critical for diagnosis and treatment guidance. Conventional assays such as serum protein electrophoresis (SPEP), immunofixation electrophoresis (SIFE), and serum-free light chain (SFLC) testing can yield discordant or inconclusive results, particularly in patients with low M-protein levels.</p><p><strong>Objectives: </strong>To evaluate the concordance and discordance between SIFE and SFLC assays in MM and to assess the clinical utility of the heavy/light chain (HLC) assay as a complementary quantitative tool.</p><p><strong>Methods: </strong>We retrospectively analyzed 1,310 MM patient samples. The concordance and discordance between SIFE and SFLC were assessed, and the analytical performance of HLC measurements was evaluated relative to conventional assays.</p><p><strong>Results: </strong>The overall discordance rate between SIFE and SFLC was 26.9%, with SIFE-/SFLC + most frequent in light chain MM and SIFE + /SFLC- observed in patients who achieved a very good partial response (VGPR). HLC strongly correlated with total immunoglobulins (combined immunoglobulin G [IgG]/immunoglobulin A [IgA], R<sup>2</sup> = 0.99) and SPEP (R<sup>2</sup> = 0.94). HLC ratios demonstrated excellent concordance with SIFE (κ = 0.83, 95% confidence interval [CI] 0.72-0.93) but poor agreement with SFLC ratios (κ = 0.01, 95% CI - 0.18-0.20). Using the HLC response model, 15 patients classified as having VGPR by the International Myeloma Working Group (IMWG) criteria were reclassified as having a partial response due to a dHLC reduction of < 90%.</p><p><strong>Conclusions: </strong>This large retrospective study provides a comprehensive evaluation of SIFE and SFLC discordance in MM, offering real-world evidence of their complementary diagnostic and monitoring roles. These findings support the integration of HLC testing into existing response assessment strategies to enhance the accuracy of treatment evaluation and the interpretation of discordant results.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypermethylation-mediated silencing of RASD1 drives multiple myeloma pathogenesis.","authors":"Chenfeng Yi, Nana Ren, Yuxi Cai, Jiajia Zhang, Yonghuai Feng","doi":"10.1007/s44313-026-00125-6","DOIUrl":"10.1007/s44313-026-00125-6","url":null,"abstract":"<p><strong>Background: </strong>The role of Ras-related dexamethasone-induced 1 (RASD1) in multiple myeloma (MM) pathogenesis remains unclear. This study investigated the expression profile, clinical significance, and epigenetic regulation of RASD1 in MM.</p><p><strong>Methods: </strong>Bone marrow samples were collected from 26 newly diagnosed patients with MM and 8 healthy controls. RASD1 messenger RNA (mRNA) and protein expression were analyzed using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry, respectively. DNA methylation status was assessed via methylation-specific PCR (MSP). The U266 MM cell line was treated with the demethylating agent decitabine (DAC) to evaluate its effects on RASD1 expression and apoptosis.</p><p><strong>Results: </strong>RASD1 mRNA and protein expression were significantly downregulated in patients with MM compared to healthy controls (P < 0.001). Low RASD1 mRNA levels correlated significantly with advanced DS stage, anemia, hypercalcemia, and elevated M-protein concentrations (P < 0.05). The receiver operating characteristic curve indicated that RASD1 mRNA expression was a robust discriminator between patients with MM and healthy individuals (area under the curve = 0.882, sensitivity = 100%, specificity = 75%). MSP analysis revealed RASD1 promoter hypermethylation in patients with MM, whereas controls exhibited hypomethylation. Treatment of U266 cells with DAC restored RASD1 expression and significantly increased apoptosis compared with controls (12.08% vs. 5.04%, P < 0.01).</p><p><strong>Conclusion: </strong>RASD1 is frequently silenced in MM through promoter hypermethylation. This epigenetic inactivation is associated with adverse clinical features and enhanced cell survival, supporting a tumor suppressor role for RASD1 in MM pathogenesis.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":" ","pages":"9"},"PeriodicalIF":2.8,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12921122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of m6A RNA methyltransferase METTL3 in drug resistance mechanisms in acute myeloid leukemia.","authors":"Suresh Prajapati, Charmi Jyotishi, Mansi Patel, Reeshu Gupta","doi":"10.1007/s44313-026-00123-8","DOIUrl":"10.1007/s44313-026-00123-8","url":null,"abstract":"<p><p>This review examines the role of METTL3, a core RNA methyltransferase, in therapeutic resistance in acute myeloid leukemia (AML) and discusses emerging strategies to address this challenge. METTL3 regulates N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modifications on transcripts involved in key cellular processes, including apoptosis (BCL2, MCL1), metabolism (PGC-1α, CSRP1), proliferation (MYC), autophagy (FOXO3), and bone marrow microenvironmental interactions (ITGA4, AKT1). These modifications enhance the stability and translation of resistance-associated genes, supporting leukemic cell survival under treatment pressure. Pharmacological targeting of METTL3 has shown efficacy in preclinical AML models. Inhibitors such as STM2457, METTL3-directed PROTACs, and rational drug combinations with agents including venetoclax, anthracyclines, and ATRA, have reversed resistance phenotypes and impaired leukemic cell fitness. Beyond canonical resistance mechanisms, METTL3 also regulates noncoding RNAs, autophagy, and metabolic-epigenetic crosstalk, including histone lactylation, linking epitranscriptomic regulation to broader resistance pathways. By integrating molecular, cellular, and microenvironmental evidence, this review underscores METTL3 as a central driver of drug resistance and a promising therapeutic target in relapsed or refractory AML. Unlike previous summaries, it highlights the convergence of METTL3-mediated m<sup>6</sup>A modifications with noncoding RNA regulation, autophagy, and niche adaptation, and critically evaluates emerging therapeutic approaches, including catalytic inhibitors, PROTACs, and natural compounds.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":"7"},"PeriodicalIF":2.8,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12858683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146087498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blood ResearchPub Date : 2026-01-22DOI: 10.1007/s44313-026-00122-9
Yoshinobu Kanda
{"title":"Propensity score analysis using the freely available user-friendly software EZR (Easy R).","authors":"Yoshinobu Kanda","doi":"10.1007/s44313-026-00122-9","DOIUrl":"10.1007/s44313-026-00122-9","url":null,"abstract":"<p><p>EZR (Easy R) is a statistical software package that is freely available on our website ( https://www.jichi.ac.jp/usr/hema/EZR/statmed.html ) and can be used on both Windows (Microsoft Corporation, USA) and macOS (Apple, USA) systems. EZR is built on R and R Commander and offers a range of statistical functions, including survival analyses with competing risks or time-dependent covariates, receiver operating characteristic curve analyses, meta-analyses, and sample size calculations, all accessible through a point-and-click graphical interface. A previous report that described the installation and basic operation of EZR (\"Investigation of the freely available easy-to-use software 'EZR' for medical statistics\", Bone Marrow Transplant, 2013) has been cited in more than 14,000 scientific papers as of November 2025. This report describes the procedures for performing propensity score (PS) analysis, including PS matching and inverse probability weighting, and compares these approaches with conventional multivariate analyses.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":" ","pages":"3"},"PeriodicalIF":2.8,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prognostic impact of smoking and alcohol consumption in male patients with diffuse large B-cell lymphoma: a multicenter retrospective study.","authors":"Ziyuan Shen, Yujin Zeng, Kang Rong, Xing Xing, Shuo Zhang, Chunling Wang, Wei Sang, Wanchuan Zhuang","doi":"10.1007/s44313-025-00120-3","DOIUrl":"10.1007/s44313-025-00120-3","url":null,"abstract":"<p><strong>Purpose: </strong>Previous studies have been inconsistent concerning the associations of smoking and alcohol consumption with the prognosis of diffuse large B-cell lymphoma (DLBCL). This study aimed to investigate the associations of smoking and drinking status with overall survival (OS) in male patients with DLBCL.</p><p><strong>Methods: </strong>A total of 371 male patients with newly diagnosed DLBCL were retrospectively enrolled from eight medical centers. Smoking and drinking status were assessed as binary variables (yes or no). Inverse probability of treatment weighting (IPTW) based on propensity scores was applied to adjust for potential confounders. Kaplan-Meier survival analysis and Cox proportional hazards models were used to assess associations.</p><p><strong>Results: </strong>Overall, 17.3% (n = 64) were smokers, and 12.7% (n = 47) reported alcohol consumption. After weighting, smoking was not associated with OS (HR = 1.192, 95% CI: 0.546-2.605, P = 0.665), nor was alcohol consumption (HR = 0.864, 95% CI: 0.174-4.288, P = 0.808). Subgroup analyses showed interactions between smoking and age (P for interaction = 0.003), and between drinking and EBV DNA status (P for interaction = 0.004). Sensitivity analyses using complete-case data and three-category exposure variables yielded consistent findings.</p><p><strong>Conclusions: </strong>In this multicenter cohort of male DLBCL patients, neither smoking nor alcohol consumption was associated with the prognosis of DLBCL. Among EBV-positive patients, alcohol use was associated with a trend toward poorer prognosis, highlighting the need for further research.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":" ","pages":"2"},"PeriodicalIF":2.8,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12808001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}