IF 21 1区医学

Blood Pub Date : 2024-11-14 DOI: 10.1182/blood.2024024187

Rebecca L Zon, Aswin Sekar, Katharine Clapham, Ohad Oren, Abhishek Niroula, Alexander G Bick, Christopher J Gibson, Gabriel Griffin, Md Mesbah Uddin, Donna Neuberg, Pradeep Natarajan, Benjamin L Ebert

{"title":"JAK2-mutant clonal hematopoiesis is associated with venous thromboembolism.","authors":"Rebecca L Zon, Aswin Sekar, Katharine Clapham, Ohad Oren, Abhishek Niroula, Alexander G Bick, Christopher J Gibson, Gabriel Griffin, Md Mesbah Uddin, Donna Neuberg, Pradeep Natarajan, Benjamin L Ebert","doi":"10.1182/blood.2024024187","DOIUrl":"10.1182/blood.2024024187","url":null,"abstract":"Abstract: Venous thromboembolism (VTE) is common among older individuals, but provoking factors are not identified in many cases. Patients with myeloid malignancies, especially myeloproliferative neoplasms (MPNs), are at increased risk for venous thrombosis. Clonal hematopoiesis of indeterminate potential (CHIP), a precursor state to myeloid malignancies, is common among older individuals and may similarly predispose to venous thrombosis. We evaluated overall and genotype-specific associations between CHIP and prevalent and incident VTE in >400 000 samples from the UK Biobank. CHIP was modestly associated with incident VTE with a hazard ratio (HR) of 1.17 (95% confidence interval [CI], 1.09-1.3; P = .002) but was not significantly associated with prevalent VTE with an odds ratio (OR) of 1.02 (95% CI, 0.81-1.23; P = .81). TET2-mutant CHIP was associated with incident VTE with a HR of 1.33 (95% CI, 1.05-1.69; P = .02). JAK2 mutations were highly associated with both prevalent and incident VTE risk, with an OR of 6.58 (95% CI, 2.65-16.29; P = 4.7 × 10-5) and a HR of 4.2 (95% CI, 2.18-8.08; P = 1.7 × 10-5), respectively, consistent with the thrombophilia associated with JAK2-mutant MPN. The association between JAK2-mutant CHIP and VTE remained significant after excluding potential undiagnosed MPN based on laboratory parameters. JAK2-mutant CHIP was more strongly associated with VTE but was less common than heterozygous factor V Leiden and heterozygous prothrombin gene mutation. These results indicate that most individuals with CHIP do not have an altered risk of thrombosis, but individuals with JAK2-mutant CHIP have a significantly elevated risk of VTE.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2149-2154"},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oxidative hemolysis due to phenazopyridine in the absence of G6PD deficiency. 在没有 G6PD 缺乏症的情况下，苯并吡啶会导致氧化溶血。

IF 21 1区医学

Blood Pub Date : 2024-11-14 DOI: 10.1182/blood.2024026349

Arielle L Langer

引用次数: 0

Imetelstat: A new addition to the Therapeutic Landscape of Lower-Risk MDS. 伊美司他低风险 MDS 治疗领域的新成员。

IF 21 1区医学

Blood Pub Date : 2024-11-14 DOI: 10.1182/blood.2024025702

Yasmin Abaza, Amy E DeZern

引用次数: 0

Ferroptosis regulates hemolysis in stored murine and human red blood cells. 铁蛋白沉积调节贮存的小鼠和人类红细胞溶血。

IF 21 1区医学

Blood Pub Date : 2024-11-14 DOI: 10.1182/blood.2024026109

Angelo D'Alessandro, Gregory R Keele, Ariel M Hay, Travis Nemkov, Eric J Earley, Daniel Stephenson, Matthew Vincent, Xutao Deng, Mars Stone, Monika Dzieciatkowska, Kirk C Hansen, Steven H Kleinman, Steven L Spitalnik, Nareg H Roubinian, Philip J Norris, Michael P Busch, Grier P Page, Brent Stockwell, Gary A Churchill, James C Zimring

{"title":"Ferroptosis regulates hemolysis in stored murine and human red blood cells.","authors":"Angelo D'Alessandro, Gregory R Keele, Ariel M Hay, Travis Nemkov, Eric J Earley, Daniel Stephenson, Matthew Vincent, Xutao Deng, Mars Stone, Monika Dzieciatkowska, Kirk C Hansen, Steven H Kleinman, Steven L Spitalnik, Nareg H Roubinian, Philip J Norris, Michael P Busch, Grier P Page, Brent Stockwell, Gary A Churchill, James C Zimring","doi":"10.1182/blood.2024026109","DOIUrl":"10.1182/blood.2024026109","url":null,"abstract":"Red blood cell (RBC) metabolism regulates hemolysis during aging in vivo and in the blood bank. However, the genetic underpinnings of RBC metabolic heterogeneity and extravascular hemolysis at population scale are incompletely understood. Based on the breeding of 8 founder strains with extreme genetic diversity, the Jackson laboratory diversity outbred population can capture the impact of genetic heterogeneity in like fashion to population-based studies. RBCs from 350 outbred mice, either fresh or stored for 7 days, were tested for post-transfusion recovery, as well as metabolomics and lipidomics analyses. Metabolite and lipid Quantitative Trait Loci (QTL) mapped >400 gene-metabolite associations, which we collated into an online interactive portal. Relevant to RBC storage, we identified a QTL hotspot on chromosome 1, mapping on the region coding for the ferrireductase Steap3, a transcriptional target to p53. Steap3 regulated post-transfusion recovery, contributing to a ferroptosis-like process of lipid peroxidation, as validated via genetic manipulation in mice. Translational validation of murine findings in humans, STEAP3 polymorphisms were associated with RBC iron content, lipid peroxidation and in vitro hemolysis in 13,091 blood donors from the Recipient Epidemiology and Donor Evaluation Study. QTL analyses in humans identified a network of gene products (FADS1/2, EPHX2, LPCAT3, SLC22A16, G6PD, ELOVL, PLA2G6) associated with lower levels of oxylipins. These polymorphisms were prevalent in donors of African descent and were linked to allele frequency of hemolysis-linked polymorphisms for Steap3 or p53. These genetic variants were also associated with lower hemoglobin increments in thousands of single-unit transfusion recipients from the vein-to-vein database.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Location, location, location: EMD in MM. 位置、位置、位置：MM 的 EMD。

IF 21 1区医学

Blood Pub Date : 2024-11-14 DOI: 10.1182/blood.2024026430

Madhav V Dhodapkar

引用次数: 0

Transplantation in adult patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: yes or no? 嗜血细胞淋巴组织细胞增多症成人患者的移植手术：可行还是不可行？

IF 21 1区医学

Blood Pub Date : 2024-11-14 DOI: 10.1182/blood.2023023287

Shuyan Yao, Lingbo He, Dina Suolitiken, Heshan Zou, Yingxin Zhu, Yini Wang

{"title":"Transplantation in adult patients with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis: yes or no?","authors":"Shuyan Yao, Lingbo He, Dina Suolitiken, Heshan Zou, Yingxin Zhu, Yini Wang","doi":"10.1182/blood.2023023287","DOIUrl":"10.1182/blood.2023023287","url":null,"abstract":"Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by aberrant immunological activity with a dismal prognosis. Epstein-Barr virus (EBV)-associated HLH (EBV-HLH) is the most common type among adults. Patients with EBV infection to B cells could benefit from rituximab, whereas lethal outcomes may occur in patients with EBV infection to T cells, nature killer cells, or multilineages. The necessity of allogeneic hematopoietic stem cell transplantation (HSCT) in adult patients with EBV-HLH remains controversial. A total of 356 adult patients with EBV-HLH entered this study. Eighty-eight received HSCT under medical recommendation. Four received salvage HSCT. The 5-year overall survival (OS) rate for patients who underwent HSCT was 48.7% (vs 16.2% in patients who did not undergo transplantation; P < .001). There was no difference in OS between patients who received transplantation at first complete response (CR1) and those at first partial response (PR1) nor between patients at CR1 and CR2. Patients who received transplantation at PR2 had inferior survival. The rate of reaching CR2 was significantly higher in patients with CR1 than PR1 (P = .014). Higher soluble CD25 levels, higher EBV-DNA loads in plasma after HSCT, poorer remission status, more advanced acute graft-versus-host disease (GVHD), and the absence of localized chronic GVHD were associated with inferior prognosis (P < .05). HSCT improved the survival of adult EBV-HLH significantly. For patients who achieved PR after initial treatment, HSCT was recommended. A wait-and-see strategy could be adopted for patients who achieved CR after initial treatment but with the risk of failing to achieve CR2.","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2107-2120"},"PeriodicalIF":21.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Handa S, Lee J-O, Derkach A, et al. Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib monotherapy. Blood. 2022;140(25):2663-2671. Handa S、Lee J-O、Derkach A 等：接受维莫非尼单药治疗的复发或难治性毛细胞白血病患者的长期疗效。Blood.2022;140(25):2663-2671.

IF 21 1区医学

Blood Pub Date : 2024-11-07 DOI: 10.1182/blood.2024026969

引用次数: 0

Endothelial inflammation: how many bad apples? 内皮炎症：有多少坏苹果？

IF 21 1区医学

Blood Pub Date : 2024-11-07 DOI: 10.1182/blood.2024026451

Michael J Simmonds

引用次数: 0

Are D+ units safe for D+ patients with anti-D? D+ 单位对抗 D 患者安全吗？

IF 21 1区医学