Blood Research最新文献

{"title":"Cold agglutinin disease: pathophysiology, diagnosis, and the evolving therapeutic landscape.","authors":"Dae-Ho Choi","doi":"10.1007/s44313-026-00169-8","DOIUrl":"10.1007/s44313-026-00169-8","url":null,"abstract":"<p><p>Cold agglutinin disease (CAD) is a rare form of autoimmune hemolytic anemia (AIHA) that accounts for approximately 15%-25% of AIHA cases and is characterized by two interdependent features: a clonal bone marrow B-cell lymphoproliferative disorder producing monoclonal immunoglobulin M (IgM)-κ autoantibodies, and complement-mediated hemolysis driven by the classical pathway. Cold agglutinins bind to erythrocytes at low temperatures and trigger C1-initiated complement activation, predominantly leading to C3b-mediated extravascular hemolysis in the liver, with intravascular hemolysis occurring chiefly during acute exacerbations. CAD must be distinguished from cold agglutinin syndrome (CAS), which occurs secondary to infection, malignant lymphoma, or other disorders, and is managed by treating the underlying cause. The 2022 World Health Organization classification recognized CAD-associated lymphoproliferative diseases as distinct entities. Beyond anemia, patients experience disabling cold-induced circulatory symptoms, profound fatigue, and elevated thromboembolic risk. Diagnosis rests on evidence of hemolysis, a monospecific direct antiglobulin test result positive for C3d but negative for immunoglobulin G (IgG), a cold agglutinin titer ≥ 1:64, and bone marrow evaluation; thermal amplitude can predict clinical severity better than titer alone. Corticosteroids and splenectomy are generally ineffective and not recommended. Contemporary management combines B-cell-directed therapy with complement inhibition, the latter being transformed by the anti-C1s antibody, sutimlimab. This review summarizes the pathophysiology, diagnostic approaches, and rapidly evolving treatment landscapes for CAD, including emerging complement- and clone-directed agents.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892284","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":"Association of the PROC rs146922325 variant with venous thrombosis in a Taiwanese population.","authors":"Chi-Yen Chen, I-Chieh Chen, Guan-Cheng Lin, Tzu-Hung Hsiao, Jiaan-Der Wang","doi":"10.1007/s44313-026-00168-9","DOIUrl":"10.1007/s44313-026-00168-9","url":null,"abstract":"<p><strong>Background: </strong>Hereditary protein C deficiency, caused by pathogenic variants in the PROC gene, is a known risk factor for venous thrombosis. However, data on PROC variants in Asian populations are limited. This study evaluated the clinical relevance of rs146922325 and its association with thrombotic outcomes in Taiwanese patients.</p><p><strong>Methods: </strong>Using genotyping data from a single-nucleotide polymorphism array as part of the Taiwan Precision Medicine Initiative, we conducted a retrospective case-control study that included 805 carriers of the PROC rs146922325 variant and 8,050 age- and sex-matched non-carriers. The baseline characteristics, coagulation profiles, and thrombotic outcomes were systematically compared. Univariable and multivariable logistic regression analyses were performed to assess the association between rs146922325 and venous thrombosis. Sensitivity analyses were conducted by restricting the cohort to warfarin-naïve participants and incident venous thrombosis events occurring after genotyping.</p><p><strong>Results: </strong>Carriers of the rs146922325 T allele exhibited significantly lower protein C levels than non-carriers (71.28% vs. 114.58%, p < 0.001) and a higher prevalence of venous thrombosis (4.10% vs. 2.48%; p = 0.009). After multivariable adjustment, rs146922325 carrier status remained independently associated with an increased risk of venous thrombosis (adjusted odds ratio [aOR], 1.61; p = 0.015). Allelic analysis further indicated that the T allele was associated with elevated thrombotic risk (aOR, 1.74; p = 0.004). No clear dose-response pattern was observed because of the limited number of homozygous TT individuals. Sex-stratified analyses suggested a similar association across sexes; however, the sex × genotype interaction was not statistically significant.</p><p><strong>Conclusion: </strong>The PROC rs146922325 variant was associated with an increased risk of venous thrombosis in the Taiwanese population. These findings expand the current knowledge of PROC-related thrombophilia in East Asians and support the potential value of genetic risk stratification in thrombosis research.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13530107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148867260","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":"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/s44313-026-00165-y","DOIUrl":"10.1007/s44313-026-00165-y","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the effectiveness, treatment durability, and infectious complications of frontline daratumumab, lenalidomide, and dexamethasone (DRd) in patients aged > 80 years with transplant-ineligible newly diagnosed multiple myeloma (Ti-NDMM) and to explore associations between baseline nutritional vulnerability and treatment outcomes.</p><p><strong>Methods: </strong>We retrospectively analyzed consecutive patients aged > 80 years with Ti-NDMM who received frontline DRd. Treatment outcomes and infectious complications were also evaluated. Exploratory analyses were performed according to baseline nutritional indices, including the Prognostic Nutritional Index (PNI) and Geriatric Nutritional Risk Index.</p><p><strong>Results: </strong>Fifteen patients were included. The overall response rate was 93.3%, and 53.3% of patients achieved a very good partial response or better. After a median follow-up of 23.1 months, the estimated median duration of treatment (DOT), time to the next treatment, and progression-free survival (PFS) were 36.7, 44.6, and 40.0 months, respectively, while the estimated median overall survival was not reached. Infectious complications, including two infection-related deaths, represented a major barrier to treatment continuation. Severe infections predominantly occurred within the first year of treatment initiation. In exploratory analyses, patients with a low baseline PNI had a shorter DOT (30.8 months vs. not reached; p = 0.049) and more frequent grade 3-5 infections (71.4% vs. 12.5%; p = 0.041).</p><p><strong>Conclusion: </strong>Frontline DRd demonstrated favorable effectiveness and clinically meaningful treatment durability in patients aged > 80 years with Ti-NDMM. Infectious complications, particularly during the early treatment period, frequently compromised the continuation of treatment. Exploratory analyses suggested that a lower baseline PNI may be associated with severe infectious complications and a shorter treatment durability.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148833272","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":"Neutropenia in adult patients with thalassemia receiving deferiprone: a 10-year experience from a large thalassemia cohort.","authors":"Ploylarp Lertvipapath, Weerapat Owatanapanich, Waratchaya Uawattanasakul, Smith Kungwankiattichai","doi":"10.1007/s44313-026-00159-w","DOIUrl":"10.1007/s44313-026-00159-w","url":null,"abstract":"<p><strong>Background: </strong>Deferiprone (DFP) is an effective oral iron chelator widely used in adult patients with thalassemia, particularly for cardiac iron removal. However, DFP is associated with rare but potentially life-threatening hematological adverse effects, notably neutropenia and agranulocytosis. Real-world data on the incidence, timing, risk factors, and outcomes of DFP-induced neutropenia in adult patients with thalassemia are limited.</p><p><strong>Purpose: </strong>To document real-life management strategies and outcomes for patients who experience neutropenia.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of adult (≥ 18 years) patients with thalassemia who initiated DFP therapy at Siriraj Hospital, Thailand, between January 2010 and December 2020. Neutropenia was defined as an absolute neutrophil count (ANC) < 1,500 cells/μL and agranulocytosis as ANC < 500 cells/μL. The incidence rates were calculated per 100 person-years. Clinical characteristics, management strategies, outcomes, and potential prognostic factors were analyzed using exploratory univariate Firth's penalized logistic regression to identify the predictors of neutropenia.</p><p><strong>Results: </strong>A total of 654 patients were included (median age 37 years; 70.8% female), predominantly with Hb E/β-thalassemia. Over 3,289.4 person-years of follow-up, nine patients developed neutropenia, including one case of agranulocytosis, yielding a cumulative incidence of 1.38% and an incidence rate of 0.27 cases per 100 person-years (95% CI 0.14-0.53). The median time to neutropenia onset was 146 d, with the highest incidence occurring within the first 6 months of therapy. One patient with agranulocytosis died from severe sepsis, corresponding to a case fatality rate of 0.03 per 100 person-years (95% CI 0.004-0.22). All patients with mild to moderate neutropenia were asymptomatic and recovered after DFP discontinuation, with a median time to resolution of 56 d. Lower baseline white blood cell (WBC) count and absolute monocyte count were associated with increased risk of neutropenia; a baseline WBC count ≤ 5,100 cells/μL demonstrated the highest predictive performance (AUC 0.86), although this estimate was derived from eight events, is optimism-corrected, and should be considered exploratory. The selected patients were rechallenged with DFP without any recurrence.</p><p><strong>Conclusion: </strong>In this large real-world cohort, DFP-induced neutropenia was uncommon but clinically significant, occurring predominantly within the first 6 months of therapy. Baseline cytopenia may help identify patients at a higher risk. With appropriate monitoring, early recognition, and individualized management, DFP remains a viable and effective iron chelation option for adult patients with thalassemia.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148819536","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":"Targeting CDK7 to overcome hypomethylating agent resistance in acute myeloid leukemia.","authors":"Bon-Kwan Koo, Eun-Ji Choi, Ju Hyun Moon, Ji Yun Kim, Hyunkyung Park, Joon Young Hur, Han-Seung Park, Yunsuk Choi, Jung-Hee Lee, Je-Hwan Lee, Eun-Hye Hur","doi":"10.1007/s44313-026-00162-1","DOIUrl":"10.1007/s44313-026-00162-1","url":null,"abstract":"<p><strong>Purpose: </strong>Hypomethylating agents (HMAs), such as azacitidine and decitabine, are widely used in elderly or medically unfit patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). However, most patients eventually develop primary or acquired resistance and outcomes following HMA failure remain poor, particularly in transplantation-ineligible patients. This study evaluated the efficacy of CDK7 inhibition as a therapeutic strategy for overcoming HMA resistance in vitro.</p><p><strong>Methods: </strong>HMA-resistant AML cells (MOLM/AZA-1 and MOLM/DEC-5) were generated to evaluate the therapeutic activity of the CDK7 inhibitor, YPN-005. Cell viability was assessed using a CellTiter-Glo assay. Western blotting was performed to examine the dysregulation of DNA methyltransferases (DNMTs) and apoptotic markers. Cell cycle distribution and apoptosis were evaluated using flow cytometry. Transcriptomic changes were analyzed using quantitative reverse transcription polymerase chain reaction.</p><p><strong>Results: </strong>YPN-005 demonstrated potent growth-inhibitory effects in HMA-resistant AML cells, with an efficacy comparable to that observed in parental MOLM-13 cells. Mechanistically, CDK7 inhibition reduced DNMT expression and decreased the phosphorylation of RNA polymerase II (Ser2/5/7). YPN-005 significantly induced apoptosis, as evidenced by increased Annexin V positivity and the activation of PARP and caspase-3. Notably, CD40 expression was markedly upregulated at both the transcript and protein levels.</p><p><strong>Conclusion: </strong>CDK7 inhibition effectively induces apoptosis in HMA-resistant AML cells by suppressing RNA polymerase II phosphorylation and downregulating aberrant DNMT expression. Furthermore, the induction of CD40 suggests a potential role for CDK7 blockade in modulating immunophenotypic features. These findings support CDK7 inhibition as a promising therapeutic strategy for overcoming resistance to epigenetic therapies in patients with AML/MDS.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148814294","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":"Feasibility of therapeutic drug monitoring of asparaginase across multiple formulations in pediatric acute lymphoblastic leukemia.","authors":"Hyery Kim, Juyeon Yu, Su Hyun Yoon, Sunghan Kang, Kyung-Nam Koh, Ho Joon Im","doi":"10.1007/s44313-026-00160-3","DOIUrl":"https://doi.org/10.1007/s44313-026-00160-3","url":null,"abstract":"","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148799240","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":"G6PD activity patterns and a stable adjusted male median derived from 16 years of clinical laboratory data.","authors":"Muhammad Shariq Shaikh, Zeeshan Ansar Ahmed","doi":"10.1007/s44313-026-00158-x","DOIUrl":"https://doi.org/10.1007/s44313-026-00158-x","url":null,"abstract":"<p><strong>Purpose: </strong>Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy worldwide, poses significant clinical and public health challenges, particularly in malaria-endemic regions. Despite the importance of quantitative G6PD activity assessments, clinically meaningful deficiency thresholds remain difficult to define owing to biological variability related to age, sex, and X-linked inheritance. The adjusted male median (AMM) is a recommended framework for defining 100% activity and deriving assay- and region-specific thresholds. However, large-scale evaluations of AMM stability and G6PD activity patterns in Pakistan are limited.</p><p><strong>Methods: </strong>We retrospectively analyzed all quantitative G6PD assays performed at a national reference laboratory in Pakistan between January 2009 and December 2024. Records with valid G6PD activity (U/g hemoglobin (Hb)), age, and sex information were included. Age- and sex-stratified distributions were examined across predefined clinical age groups. The calculated AMM was based on adult males aged 18-45 years (excluding those with ≤ 10% of the initial median). Sensitivity analyses were used to assess AMM stability across alternative adult male age windows (15-50 and 18-60 years). The G6PD activity categories were defined as severe (< 10%), moderate (10-30%), intermediate (30-60%), and normal (> 60%) relative to the AMM.</p><p><strong>Results: </strong>In total, 51,748 specimens (41,397 from males and 10,351 from females) were analyzed. The median (interquartile range) G6PD activity was 10.3 (7.8-12.6) U/g Hb among males and 10.7 (8.5-12.9) U/g Hb among females. The AMM derived from 7,436 adult males was 9.2 U/g Hb and remained highly stable across alternative age windows (9.2-9.3 U/g Hb; ~ 1% variation). Based on AMM thresholds, 15.4% (95% CI: 15.1-15.7%) of the tested population had < 60% activity, including 6.8% with severe and 4.9% with moderate deficiency. G6PD activity was highest in neonates and infants and declined progressively with age.</p><p><strong>Conclusions: </strong>The locally derived AMM provides a robust reference standard that reflects the enzymatic capacity within the specific clinical catchment area and serves as a foundation for future clinical validation studies. Age- and sex-specific activity patterns aligned with known physiological and genetic determinants. Although this study provided a locally validated laboratory reference framework, prospective studies correlating the enzymatic categories with clinical outcomes and genotypic data are needed before its broader clinical or public health implementation.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13476390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765810","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":"Clonal hematopoietic mutations as a predictor of adverse outcomes in cytopenic patients with chronic kidney disease.","authors":"Suwannaporn Yaophrukchai, Chantana Polprasert, Sirorat Kobbuaklee, Ponlapat Rojnuckarin, Sunisa Kongkiatkamon","doi":"10.1007/s44313-026-00161-2","DOIUrl":"10.1007/s44313-026-00161-2","url":null,"abstract":"<p><strong>Purpose: </strong>Clonal hematopoiesis (CH) is associated with cardiovascular disease (CVD), inflammation, and increased mortality. However, its prevalence and clinical impact in patients with cytopenia and chronic kidney disease (CKD) remain unclear.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of patients with cytopenia and CKD who underwent targeted sequencing to evaluate the association between CH, CKD progression, and overall mortality.</p><p><strong>Results: </strong>A total of 67 patients were included (mean age 75.7 ± 10.5 years; 58.2% male). Most patients had myelodysplastic neoplasms (MDS) (79.1%), followed by clonal cytopenia of undetermined significance (CCUS) and idiopathic cytopenia of undetermined significance (ICUS) (14.9%). CH was detected in 53.7% of the patients, most commonly involving TET2 (44.4%), DNMT3A (22.2%), and ASXL1 (22.2%). Over a median follow-up of 43.5 months (interquartile range [IQR] 34.3-79.3), CKD progression occurred in 34.3%. The 5-year cumulative incidence of CKD progression tended to be higher in the CH carriers than in the non-carriers (55.4% vs. 31.4%; log-rank p = 0.066). In multivariable Cox analysis, CH remained independently associated with CKD progression (adjusted hazard ratio [HR] 2.83; 95% confidence intervals [CI] 1.03-7.79; p = 0.044). CKD progression was most frequent in patients with MDS and CH (46%), followed by MDS without CH (30%) and CCUS (16%), with no progression in ICUS. Mortality was higher in CH carriers (50.0% vs. 16.1%; p = 0.004) and remained independently associated with CH (adjusted HR 3.90; 95% CI 1.41-10.83; p = 0.009).</p><p><strong>Conclusions: </strong>CH is common in cytopenic patients with CKD and is independently associated with an increased risk of CKD progression and mortality. The assessment of CH may improve risk stratification and identify high-risk patients with adverse renal and survival outcomes.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725969","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":"Deciphering the circadian signature in acute myeloid leukemia: NPAS2 downregulation as a master predictive feature.","authors":"Leidivan Sousa da Cunha, Guilherme Passos de Morais, Caio Bezerra Machado, Deivide de Sousa Oliveira, Beatriz Maria Dias Nogueira, Anna Karolyna da Costa Machado, Isabelle Magalhães Farias, Flávia Melo Cunha de Pinho Pessoa, Rodrigo Monteiro Ribeiro, Kaira Mara Cordeiro de Alburquerque, Mateus de Paula Gomes, Manoel Odorico de Moraes Filho, Maria Elisabete Amaral de Moraes, Caroline Aquino Moreira-Nunes","doi":"10.1007/s44313-026-00157-y","DOIUrl":"10.1007/s44313-026-00157-y","url":null,"abstract":"<p><strong>Purpose: </strong>Considering the role of circadian clock genes in leukemogenesis through the regulation of cell cycle progression and genomic stability, this study aimed to evaluate the expression of NPAS2, CIPC, BMAL1, and CLOCK in acute myeloid leukemia (AML) and to determine their individual and combined diagnostic performance.</p><p><strong>Methods: </strong>In this study, bone marrow (BM) and peripheral blood (PB) samples were obtained from newly diagnosed AML patients and healthy controls under standardized circadian conditions. Gene expression was measured by TaqMan RT-qPCR and normalized to ABL using the 2^ΔΔCt method. Diagnostic performance was evaluated by ROC analysis and multivariate logistic regression, and a random forest classifier with SHAP-based feature importance was applied to assess predictive contribution of each gene.</p><p><strong>Results: </strong>PB showed comparable expression levels to paired BM samples, supporting its use as a surrogate tissue for circadian biomarker assessment. All transcripts were significantly downregulated in AML compared with controls (p < 0.001), with NPAS2 showing the most pronounced reduction. NPAS2 exhibited the highest diagnostic performance (AUC = 0.925). The random forest classifier achieved 74% sensitivity and 100% specificity, and SHAP analysis identified NPAS2 as the most influential predictive feature.</p><p><strong>Conclusion: </strong>As such, we propose downregulation of NPAS2 as a potential biomarker for diagnosis of AML.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13468828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148722974","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":"Myeloid-lineage blasts with histiocytoid differentiation in TP53 mutated acute myeloid leukemia: a deceptive morphologic overlap with mature malignant histiocytic neoplasms.","authors":"Neha Seth, Aishwarya Ravindran","doi":"10.1007/s44313-026-00156-z","DOIUrl":"10.1007/s44313-026-00156-z","url":null,"abstract":"<p><p>Here, we report a case of TP53-mutated acute myeloid leukemia (AML) with monocytic differentiation that showed striking histiocytoid morphologic transformation following induction chemotherapy. Post-treatment blasts demonstrated significant morphologic overlap with mature malignant histiocytic neoplasms, particularly histiocytic sarcoma subtype, creating a potential diagnostic pitfall. Retained myeloperoxidase expression, together with the absence of cyclin D1 expression, supported a diagnosis of persistent AML rather than divergent histiocytic differentiation.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"61 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664665","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}