Blood Research最新文献

{"title":"Telomere length analysis using qPCR in aplastic anemia: prevalence and predictive value for germline mutation status.","authors":"Sudhanshi Raina, Arihant Jain, Venus Thakur, Anand Balakrishnan, Manu Jamwal, Prateek Bhatia, Deepak Bansal, Pankaj Malhotra, Reena Das, Sreejesh Sreedharanunni","doi":"10.1007/s44313-026-00182-x","DOIUrl":"https://doi.org/10.1007/s44313-026-00182-x","url":null,"abstract":"<p><strong>Purpose: </strong>Telomere length analysis (TLA) is used to identify telomere biology disorders (TBD) in aplastic anemia (AA); however, the diagnostic performance of quantitative PCR (qPCR)-based TLA across germline mutation categories remains poorly defined.</p><p><strong>Methods: </strong>A total of 305 consecutive patients with AA were prospectively enrolled over 3.5 years. All patients underwent age-adjusted qPCR-based TLA and comprehensive germline sequencing, including whole exome sequencing or blended genome-exome sequencing, and were classified as having inherited bone marrow failure syndrome (IBMFS) (Category 1, n = 40), a monoallelic carrier state (Category 2, n = 19), a variant of uncertain significance (VUS; Category 3, n = 39), or AA without germline variants (Category 4, n = 207).</p><p><strong>Results: </strong>Shortened telomere length (TL) (≤ 10th percentile) was present in 37.7% of patients, and very short TL (≤ 1st percentile) was present in 14.8%. The degree of shortening varied by etiology: 71.4% of confirmed TBD gene carriers had shortened TL compared with 31.6% of carriers of biallelic variants in Fanconi anemia pathway genes and 37.7% of patients with acquired AA. TL did not distinguish confirmed IBMFS from acquired AA across the full disease spectrum; however, normal TL (> 10th percentile) excluded TBD-associated IBMFS (TBD-IBMFS) with a negative predictive value of 98.5%. Very short TL (≤ 1st percentile) had a positive predictive value of only 12.9% for TBD-IBMFS and was also observed in 13.0% of acquired-AA patients.</p><p><strong>Conclusions: </strong>In unselected patients with AA, qPCR-based TLA does not distinguish inherited from acquired disease across the full spectrum of IBMFS; however, normal TL substantially lowers the likelihood of TBD-IBMFS. Very short TL is not specific to constitutional telomeropathy and should be interpreted with caution when adjudicating TBD variants of uncertain significance.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149116317","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":"Unveiling the role of circulating monocyte-macrophage polarization state and PD-L1/PD-L2 expression in newly diagnosed pediatric ITP.","authors":"Asmaa M Zahran, Omnia El-Badawy, Mervat A M Youssef, Mena Sameh Yousef Ghattas, Maha H Mohamed, Salma G Morsy, Khalid I Elsayh, Hossam Elashmawy, Zeinab Albadry M Zahran","doi":"10.1007/s44313-026-00163-0","DOIUrl":"https://doi.org/10.1007/s44313-026-00163-0","url":null,"abstract":"<p><strong>Background: </strong>Immune thrombocytopenia (ITP) is an immune-mediated disorder characterized by decreased platelet count resulting from immune dysregulation and altered cellular immune responses. This study aimed to evaluate monocyte-macrophage polarization patterns and the expression of immune checkpoint molecules CD273 (PD-L2) and CD274 (PD-L1) in patients with ITP and explore their association with hematological parameters and response to corticosteroid therapy.</p><p><strong>Methods: </strong>This case-control study compared patients with primary ITP and healthy controls. Hematological indices were assessed using complete blood counts, and monocyte-macrophage subsets including M1-like and M2-like populations and their subtypes (M2a, M2b, and M2c), along with CD273 and CD274 expression were analyzed by flow cytometry.</p><p><strong>Results: </strong>Patients with ITP showed significantly lower hemoglobin levels, platelet counts, and lymphocyte counts, with higher mean platelet volume (MPV) and platelet distribution width (PDW) compared with controls. A marked increase in M1-like monocyte-macrophages with a concomitant reduction in total M2-like cells was observed in patients with ITP. Within M2 subsets, M2a-like cells were increased, whereas M2b-like and M2c-like subsets were decreased. Expression of CD273 and CD274 were reduced on M1-like cells, and CD273 expression was significantly decreased on M1-like and M2a-like subsets only, with non-significant trends in M2b-like cells. Non-responders to corticosteroid therapy demonstrated higher M1 polarization, increased M2a levels, reduced M2b and M2c subsets, and lower CD273 expression among M1 and M2a compared with responders. Significant correlations were identified between macrophage-like subsets and platelet count, hemoglobin, MPV, and PDW.</p><p><strong>Conclusion: </strong>These findings suggested that a pro-inflammatory M1-like polarization shift combined with an impaired dual PD-L1/PD-L2 checkpoint expression on M2b-like macrophages are significantly correlated with platelet indices and collectively contribute to ITP immunopathogenesis and treatment response, supporting macrophage polarization as a promising immunomodulatory target.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149116338","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":"Ferroptosis-related genes influence AML risk through immune cell-mediated pathways: a Mendelian randomization study with mediation analysis.","authors":"Qi Meng, Zihao Zhou, Wanchao Zhang","doi":"10.1007/s44313-026-00166-x","DOIUrl":"10.1007/s44313-026-00166-x","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is driven by complex interactions among genetic alterations, metabolic reprogramming, and immune microenvironment dysregulation. Ferroptosis, a form of iron-dependent regulated cell death linking iron metabolism with immune regulation, has been implicated in AML; however, its causal interplay with immune cells remains unclear. Therefore, this study employed a Mendelian randomization (MR) approach to systematically investigate this relationship.</p><p><strong>Methods: </strong>We conducted a two-sample MR study to investigate the causal effects of ferroptosis-related genes and immune cell subsets on AML risk. Ferroptosis-related genes were obtained from the FerrDb database; corresponding expression quantitative trait loci from the GTEx project were used as instrumental variables. Summary-level genome-wide association study (GWAS) data for AML served as the outcome, and immune cell traits were derived from publicly available immunophenotype GWAS datasets. The inverse variance-weighted method was applied as the primary MR approach, followed by sensitivity analyses. Mediation analyses were performed to quantify the role of immune cells in gene-AML associations.</p><p><strong>Results: </strong>Several ferroptosis-related genes, including SLC40A1, SIRT1, BCAT2, RPL8, and CREB5, were significantly associated with AML risk. Multiple myeloid immune cell subsets mediated part of these effects. No significant heterogeneity or horizontal pleiotropy was observed.</p><p><strong>Conclusions: </strong>This study provides genetic evidence that ferroptosis-related genes influence AML risk, directly and indirectly, through specific immune cell populations, highlighting the ferroptosis-immune axis as a potential target for AML stratification and therapy.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13593998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018215","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":"Expanding the spectrum of post-HSCT hemolysis: from passenger lymphocyte syndrome to host- and graft-associated alloimmune hemolytic anemia.","authors":"Dong Wook Jekarl, Jungjun Lee, Yujin Cha, Jay Ho Han, Seung Hee Cho, Jihyang Lim, Yonggoo Kim","doi":"10.1007/s44313-026-00173-y","DOIUrl":"10.1007/s44313-026-00173-y","url":null,"abstract":"<p><p>Immune-mediated alloimmunization and hemolytic anemia can complicate ABO-incompatible hematopoietic stem cell transplantation (HSCT). After major ABO-incompatible HSCT, clinical manifestations may include pure red cell aplasia and delayed hemolysis. Passenger lymphocyte syndrome and delayed hemolysis are typical complications of minor ABO-incompatible HSCT. Because delayed hemolysis after major or minor ABO mismatch may be indistinguishable, the terms host-associated alloimmune hemolytic anemia and graft-associated alloimmune hemolytic anemia have been tentatively proposed to distinguish these conditions according to their host or graft origin. However, the rarity of these subgroups may limit the clinical utility of this classification. Management across the clinical spectrum includes transfusion support, plasmapheresis, and therapeutics related to immunomodulatory therapies.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13582783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983798","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":"High-risk features in adult patients with B-cell acute lymphoblastic leukemia: redefining risk in the era of targeted immunotherapy.","authors":"Dong Won Baek","doi":"10.1007/s44313-026-00175-w","DOIUrl":"10.1007/s44313-026-00175-w","url":null,"abstract":"<p><p>The treatment landscape of adult B-cell acute lymphoblastic leukemia (B-ALL) has changed substantially with the introduction of targeted immunotherapeutic agents. Historically, high-risk disease was defined by clinical and cytogenetic features such as older age, elevated leukocyte count, and Philadelphia chromosome (Ph)-positive status. Advances in genomic profiling, together with the use of next-generation tyrosine kinase inhibitors, bispecific T-cell engagers, antibody-drug conjugates, and chimeric antigen receptor T-cell therapies, have altered both treatment outcomes and risk stratification. Outcomes for patients with Ph-positive B-ALL have improved markedly, particularly with ponatinib- and blinatumomab-based regimens, but several molecularly defined subgroups continue to have poor prognoses. These include IKZF1^plus Ph-positive B-ALL, TP53-mutated and hypodiploid B-ALL, Ph-like B-ALL, and KMT2A-rearranged B-ALL. Emerging evidence indicates that introducing immunotherapeutic agents early in treatment can improve response quality and rates of measurable residual disease negativity, including in patients with high-risk disease. Relapse nevertheless remains a major challenge, and the optimal integration of novel agents, allogeneic hematopoietic cell transplantation, and cellular immunotherapy remains uncertain. This review summarizes the biological and clinical features of the major high-risk molecular subgroups of adult B-ALL and discusses how recent therapeutic advances are redefining risk assessment and treatment strategies in the era of targeted immunotherapy.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978265","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":"Correction: Frontline daratumumab, lenalidomide, and dexamethasone in patients older than 80 years with newly diagnosed multiple myeloma: treatment durability, infectious complications, and nutritional vulnerability.","authors":"Yuichi Horigome, Koichi Ehata, Noriyuki Tadera, Kei Hayama, Hirotoshi Kamata, Takahiro Suzuki, Koji Miyazaki","doi":"10.1007/s44313-026-00178-7","DOIUrl":"10.1007/s44313-026-00178-7","url":null,"abstract":"","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148971632","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":"Limited evidence for causal effects of circulating inflammatory cytokines on the risk of selected hematologic malignancies: a two-sample Mendelian randomization study.","authors":"Huimin Zhang, Lihong Zhang, Dan Zhao, Bing Ma, Jianying Wang, Xinying Liu, Wanyi Yin, Yang Shen, Liu Yang, Wen Dong, Cuiyu Wang","doi":"10.1007/s44313-026-00164-z","DOIUrl":"10.1007/s44313-026-00164-z","url":null,"abstract":"<p><strong>Background: </strong>Hematologic malignancies have been linked to inflammatory cytokine levels; however, whether a causal relationship exists between inflammatory cytokines and hematologic malignancies remains uncertain. This study aimed to explore the causal association between inflammatory cytokines and hematologic malignancies using Mendelian randomization (MR) analysis.</p><p><strong>Methods: </strong>Summary statistics from genome-wide association studies of 41 inflammatory cytokines, C-reactive protein, and selected hematologic malignancies were obtained from the UK Biobank, YFS, FINRISK, and FinnGen consortia. The inverse-variance weighted (IVW) method with false discovery rate (FDR) adjustment was used as the primary MR method. The weighted median, MR-Egger regression, MR-Robust Adjusted Profile Score, and MR pleiotropy residual sum, and outlier methods were used as supplied analyses. MR-Egger intercept estimates and Cochran's Q test were used to assess pleiotropy and heterogeneity. Leave-one-out analysis and the MR Steiger test were used to assess sensitivity and the direction of causality.</p><p><strong>Results: </strong>Although the primary IVW analysis indicated that some inflammatory cytokines were associated with risk of selected hematologic malignancies, no significant causal relationship between cytokines and selected hematologic malignancies was detected after FDR correction.</p><p><strong>Conclusion: </strong>Genetically predicted cytokine levels did not have a significant effect on the risk of the selected hematologic malignancies. Further research is warranted to confirm the potential association between cytokine levels and the risk of selected hematologic malignancies.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945983","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":"Daratumumab monotherapy for relapsed AL amyloidosis: a single center retrospective analysis.","authors":"Jun Ho Yi, Sang Eun Yoon, Seok Jin Kim, Darae Kim, Jin-Oh Choi, Ju-Hong Min, Byoung Joon Kim, Jung-Sun Kim, Jung Eun Lee, Junseok Jeon, Joon Young Choi, Kihyun Kim","doi":"10.1007/s44313-026-00174-x","DOIUrl":"10.1007/s44313-026-00174-x","url":null,"abstract":"<p><strong>Purpose: </strong>Treatment of relapsed AL amyloidosis remains challenging as patients frequently suffer from severe organ dysfunctions. Daratumumab, a cornerstone drug in multiple myeloma and newly diagnosed AL amyloidosis, has also shown promise in relapsed AL amyloidosis.</p><p><strong>Materials and methods: </strong>To assess the efficacy of daratumumab, we conducted a retrospective study of 40 patients who received daratumumab monotherapy in our prospective amyloidosis cohort.</p><p><strong>Results: </strong>The median age of the cohort was 67 years, and 31 patients were classified as stage III/IV by the Mayo 2012 guidelines and 32 patients as stage IIIa/IIIb by the European staging system. The overall hematologic and cardiac response rates were 72.5% and 42.4%, respectively. With median follow-up duration of 26.9 months, the estimated median progression-free survival was 21.9 months. Deep hematologic (p < 0.001) and cardiac response (p = 0.001) were associated with prolonged progression free survival. The duration of hematologic/cardiac responses were 26.2 months and 27.8 months, respectively. The median overall survival was 30.9 months. Treatment was well tolerated, as with 3 patients experiencing grade 3-4 hematologic adverse events and 8 experiencing grade 3-4 non-hematologic adverse events.</p><p><strong>Discussion: </strong>Our findings suggest that daratumumab monotherapy provides rapid and durable responses and is generally well tolerated in patients with relapsed AL amyloidosis.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931521","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":"CRS and ICANS: Early detection and personalized management.","authors":"Jinchul Kim","doi":"10.1007/s44313-026-00167-w","DOIUrl":"10.1007/s44313-026-00167-w","url":null,"abstract":"<p><p>T-cell-redirected immunotherapies, including chimeric antigen receptor T-cell therapy and bispecific antibodies, have transformed the treatment of relapsed or refractory hematologic malignancies. However, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remain the major immune-mediated toxicities that can complicate treatment delivery and contribute to morbidity and non-relapse mortality. CRS is characterized by systemic inflammatory amplification involving activated T cells, tumor cells, monocytes/macrophages, endothelial activation, and cytokine networks. ICANS is biologically related to CRS but has distinct features, including endothelial injury, blood-brain barrier disruption, and central nervous system inflammation. Standardized grading systems and structured neurologic assessments provide a common framework for recognition; however, optimal care increasingly requires risk-adapted and individualized strategies. Baseline disease burden, systemic inflammation, endothelial vulnerability, organ reserve, treatment platform, and product-specific toxicity profiles may help identify patients requiring closer monitoring or earlier intervention. Although prediction models and emerging monitoring approaches may improve early recognition, their roles should complement rather than replace clinical judgment. Management should balance timely toxicity control with the preservation of antitumor efficacy, avoidance of excessive immunosuppression, and careful attention to infection and cytopenia risks. For refractory CRS or ICANS, phenotype-directed escalation and multidisciplinary care are essential. This review summarizes the current concepts in the biology, recognition, risk prediction, early detection, and personalized management of CRS and ICANS.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921005","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":"FLT3-mutated AML: standards of care and ongoing investigation.","authors":"Ly V Do, Jessica J Jorgensen, Kieran D Sahasrabudhe","doi":"10.1007/s44313-026-00171-0","DOIUrl":"10.1007/s44313-026-00171-0","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is characterized by the rapid, unchecked clonal proliferation of myeloid precursor cells. It is the most common type of acute leukemia in adults and exhibits significant molecular heterogeneity. FLT3 mutations are among the most common and well-described genetic mutations in AML; they worsen overall survival and increase the relapse rate. Treatment options for FLT3-mutated AML are rapidly expanding, with an increasing number of FLT3 inhibitors being incorporated into treatment regimens. This review provides an overview of the role of FLT3 inhibitors in the current standard of care therapy in both the newly diagnosed and relapsed/refractory settings. Additionally, it highlights the areas of key ongoing investigations in the treatment of FLT3-mutated AML.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913734","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}