Blood最新文献

{"title":"Untangling the ties that bind: the NG2-ITGA4 axis in B-ALL.","authors":"Chun Shik Park, Charles G Mullighan","doi":"10.1182/blood.2026035164","DOIUrl":"https://doi.org/10.1182/blood.2026035164","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"148 16","pages":"1952-1954"},"PeriodicalIF":23.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191128","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}

{"title":"Ironing out vascular control in anemia.","authors":"Adam J Case","doi":"10.1182/blood.2026035300","DOIUrl":"10.1182/blood.2026035300","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"148 16","pages":"1959-1960"},"PeriodicalIF":23.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Consequences and Targeting of PPM1D Overexpression in Myeloproliferative Neoplasms.","authors":"Md Babu Mia, Christoph Schaniel, Cara Clementelli, Sarah Elisabeth Haines, Malgorzata Olszewska, JoAnn Arandela, Sebastian Elghaity-Beckley, Sophie Klingborg, Zinedine Hoque, Ayman Mohammad, Shwetha Hara Sridhar, Brianna Kelly, Xiaoli Wang, Emmanuel Olivier, Alan H Shih, Blake T Langlais, Allison Cote, Noushin Farnoud, Raajit K Rampal, Duke Butterfield, Amylou C Dueck, Min Lu, Kristin G Beaumont, Robert Sebra, John O Mascarenhas, Eirini P Papapetrou, Ronald Hoffman, Bridget K Marcellino","doi":"10.1182/blood.2025030377","DOIUrl":"https://doi.org/10.1182/blood.2025030377","url":null,"abstract":"<p><p>Phosphatase Mg2+/Mn2+ dependent 1D protein (PPM1D) is a serine threonine phosphatase known to regulate oncogenic pathways. PPM1D mutations are enriched in therapy-related MDS and AML, but the role of PPM1D in myeloproliferative neoplasms (MPN) remains largely unexplored. By sequencing 519 MPN patients, we detected activating PPM1D mutations in 3.1% of them. Importantly, PPM1D was overexpressed in hematopoietic stem and progenitor cells (HSPCs) in most PPM1D wild-type (WT) MPN cases. To elucidate the impact of PPM1D mutations on MPN HSPCs, we generated isogenic JAK2V617F+/PPM1D-WT and JAK2V617F+/PPM1D mutant (MUT) induced pluripotent stem cell (iPSC) lines from a MPN patient. Single-cell RNA-sequencing (scRNA-seq) of iPSC derived HSPCs revealed altered TP53, DNA damage response and cell cycle regulation. scRNA-seq analysis of primary PPM1D-MUT MPN patient mononuclear cells (MNCs) further confirmed upregulation of MYC, mTORC1, OXPHOS, JAK/STAT, and NF-κB pathways and corresponding genes in HSCs. The allosteric PPM1D inhibitor (PPM1Di) GSK2830371 preferentially inhibited colony formation in myelofibrosis (MF) samples. Combination treatment of GSK2830371 with low dose inhibition of HDM2, a negative regulator of p53, significantly improved targeting of JAK2V617F+ HSPCs, while sparing normal HSPCs. Single-cell mutational and protein analysis of a clonally complex MF patient sample treated with this combination strategy revealed reduced mutated clones and increased WT clones by >4-fold. Dual PPM1D and HDM2 targeting also significantly decreased leukemic burden in a xenograft MPN model. These findings support PPM1D as a critical MPN HSPCs regulator and support dual PPM1D/HDM2 inhibition as a treatment strategy for MF patients.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179341","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}

{"title":"Germline DDX41 defines a distinct subgroup in MDS undergoing transplantation with reduced relapse and improved survival.","authors":"Nico Gagelmann, Christopher R Reilly, Archana Sasi, Kyle Hebert, Paul Auer, Jing Dong, Tao Zhang, Tao Wang, Corey S Cutler, Robert J Soiffer, Stephen R Spellman, Wael Saber, R Coleman Lindsley","doi":"10.1182/blood.2026034923","DOIUrl":"10.1182/blood.2026034923","url":null,"abstract":"<p><p>Germline DDX41 variants are a recognized cause of adult myelodysplastic neoplasms (MDS), characterized by distinct biological features and favorable prognosis. The independent effect of DDX41 status on outcomes after allogeneic transplantation, the role of conditioning intensity, and treatment-related toxicity risk remain unresolved. To address this gap, we analyzed 1,514 patients with MDS undergoing transplantation prior to routine DDX41 testing alongside a wild-type comparator, providing an unbiased benchmark for this molecular subgroup. Forty-nine patients (3.2%) carried pathogenic/likely pathogenic (P/LP) germline DDX41 variants; 19 (39%) had an additional somatic DDX41 mutation, most commonly p.R525H. P/LP DDX41 cases were older (median 63 vs 59 years) and showed lower IPSS-M risk with absent TP53 mutations (0% vs 21%). In terms of outcome, 2-year relapse incidence was significantly lower in P/LP DDX41 (17% vs 34%, p=0.01). In multivariable analysis, the presence of a DDX41 P/LP variant independently associated with lower risk of relapse (hazard ratio 0.43, 95% CI 0.21-0.88; p=0.02), concentrated in the reduced-intensity/nonmyeloablative stratum. Adjusted models showed significantly improved disease-free survival (DFS) for P/LP DDX41 (hazard ratio 0.62, 95% CI 0.41-0.95; p=0.03) and no significant association with non-relapse mortality (NRM) or graft-versus-host disease (GVHD). In summary, these findings identify DDX41-associated MDS as a transplant subgroup with superior DFS regardless of conditioning intensity driven by reduced relapse risk and lack of excess NRM and GVHD supporting incorporation of germline DDX41 status into transplant planning.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179331","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}

{"title":"Ambient oxygen disrupts amino acid homeostasis and impairs human hematopoietic stem and progenitor cell engraftment.","authors":"Xuepeng Wang, Sankalp Srivastava, Rahul Kanumuri, Ramesh Kumar, Minghua Zhong, Ji Zhang, Reuben Kapur","doi":"10.1182/blood.2026034288","DOIUrl":"https://doi.org/10.1182/blood.2026034288","url":null,"abstract":"<p><p>Hematopoietic stem cell transplantation is limited not only by donor cell number and recipient conditioning, but also by loss of stem-cell fitness during collection and processing. Hematopoietic stem and progenitor cells normally reside in a physiologically hypoxic marrow environment, yet routine ex vivo handling exposes them to ambient oxygen outside this niche. Although ambient oxygen exposure during ex vivo handling impairs hematopoietic stem cell (HSC) function, the metabolic basis for this effect remains incompletely defined. Using hypoxic handling as a physiologic reference, we examined whether functionally relevant consequences of ambient oxygen exposure remain modifiable in human CD34+ cells during ex vivo handling. Quantitative LC-MS profiling revealed that ambient oxygen exposure rapidly increased intracellular amino acids, including branched-chain amino acids, together with activation of nutrient-sensing pathways. This metabolic shift was associated with increased mTORC1 signaling, attenuation of lysosomal programs, and impaired primary and secondary engraftment. Complementary single-cell analyses supported a coordinated transition toward nutrient-activated states under ambient oxygen, whereas hypoxia preserved relative metabolic restraint. Transient restriction of essential amino acids or branched-chain amino acids during ex vivo handling restored lysosomal programs and improved engraftment of normoxia-handled human CD34+ cells. Pharmacologic LAT1 inhibition similarly improved engraftment. Together, these findings identify disruption of amino acid homeostasis as a previously underappreciated consequence of ambient oxygen exposure during routine ex vivo handling and demonstrate that a functionally relevant component of this injury remains modifiable after exposure to improve human HSPC engraftment.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":23.9,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179265","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}

{"title":"PD-L1: the sinister edge of the TGF-β double-edged sword.","authors":"Áron Pánczél, Attila Mócsai","doi":"10.1182/blood.2026034638","DOIUrl":"https://doi.org/10.1182/blood.2026034638","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"148 15","pages":"1864-1866"},"PeriodicalIF":23.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135115","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}

{"title":"Seeing the myeloma bone marrow through an ecological lens.","authors":"Kwee L Yong","doi":"10.1182/blood.2026035510","DOIUrl":"https://doi.org/10.1182/blood.2026035510","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"148 15","pages":"1862"},"PeriodicalIF":23.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135085","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}

{"title":"Muffly L, Frey NV, Roloff GW, et al. Consensus recommendations for CAR T-cell administration in adult acute lymphoblastic leukemia: a modified Delphi study. Blood. 2026;148(6):657-668.","authors":"","doi":"10.1182/blood.2026036233","DOIUrl":"https://doi.org/10.1182/blood.2026036233","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"148 15","pages":"1941"},"PeriodicalIF":23.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135056","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}

{"title":"Human HSPC clones balance stochastic diversification with cytokine-induced differentiation.","authors":"Elia Colin, Dror Brook, Jonathan Izraeli, Oren Milman, Aviezer Lifshitz, Tal Bacharach, Noa Chapal-Ilani, Liran Shlush, Amos Tanay","doi":"10.1182/blood.2026033834","DOIUrl":"10.1182/blood.2026033834","url":null,"abstract":"<p><strong>Abstract: </strong>Hematopoietic stem and progenitor cells (HSPCs) balance self-renewal with on-demand differentiation of blood lineages. Modern bone marrow atlases specify static transcriptional states, but not HSPC dynamics, which are only partly understood, particularly in humans. Here, we introduce cHSPCTrack (clonal HSPC tracker), an in vitro framework for serially tracking clonal differentiation and fate acquisition from human HSPCs extracted from circulation. By following thousands of single-cell-derived clones stimulated by different cytokine combinations, cHSPCTrack reconstructs the balance between stochasticity and directed differentiation in human HSPCs. Single HSPCs stochastically yield multiple lineages under a uniform cytokine environment, with stimulatory inputs modulating differentiation probabilities by introducing biases toward preferred fates. In parallel, differentiation rates vary stochastically across and within clones. Clonal memory stabilizes the induction of a few genes per clone over otherwise archetypal differentiation trajectories. Within clones, multiple fates can interact with each other, as shown for clones mixing basophils, eosinophils, and mast cells with other fates. cHSPCTrack opens avenues for understanding hematopoietic clonal dynamics in health and disease.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"1880-1892"},"PeriodicalIF":23.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood stem cell fate: balancing chance and cues.","authors":"Simon Haas","doi":"10.1182/blood.2026035513","DOIUrl":"https://doi.org/10.1182/blood.2026035513","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"148 15","pages":"1860-1862"},"PeriodicalIF":23.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135140","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}