Blood advances最新文献

{"title":"Factors associated with survival after allogeneic transplantation for myeloid neoplasms harboring TP53 mutations.","authors":"Anmol Baranwal, Kimberly J Langer, Vedavyas Gannamani, Danielle Rud, Alia Cibich, Caner Saygin, Mariam Nawas, Talha Badar, Mohamed A Kharfan-Dabaja, Ernesto Ayala, Vivek Roy, James M Foran, Hemant S Murthy, Madiha Iqbal, Jeanne Palmer, Lisa Z Sproat, Saurabh Chhabra, Nandita Khera, Mehrdad Hefazi, Abhishek Mangaonkar, William Hogan, Mark Litzow, Hassan Alkhateeb, Ayalew Tefferi, Chung Hoow Kok, Guru Subramanian Guru Murthy, Anand Patel, Ashish Bajel, Devendra K Hiwase, Mithun Vinod Shah","doi":"10.1182/bloodadvances.2024015335","DOIUrl":"10.1182/bloodadvances.2024015335","url":null,"abstract":"<p><strong>Abstract: </strong>Allogeneic hematopoietic stem cell transplant (alloHCT) is considered for all patients with myeloid neoplasms (MNs) harboring TP53 mutations (TP53mut). The aim of this international study across 7 transplant centers in the United States and Australia was to identify factors associated with improved post-alloHCT survival. Of 134 TP53mut MN cases who underwent alloHCT, 80% harbored complex karyotype; 94% of TP53 variants were localized to the DNA-binding domain (DBD). Most common comutations were ASXL1 (7%), TET2 (7%), and DNMT3A (6%). Median post-HCT survival was 1.03 years, and overall survival (OS) at 1 year, 2 years, and 3 years was 51.4%, 35.1%, and 25.1%, respectively. A total of 103 cases (76.9%) met the International Consensus Classification (ICC) criteria for MN with mutated TP53 (referred to as ICC-defined TP53mut MN hereafter). The 3-year OS of ICC-defined TP53mut was significantly shorter compared with that of other TP53mut MNs (3-year OS, 16.9% vs 54.9%; P = .002). ICC-defined TP53mut MNs was independently associated with inferior OS (hazard ratio [HR], 2.62; P = .019). The presence of non-DBD TP53mut only (HR, 3.40; P = .005), DNMT3A comutation (HR, 2.64; P = .016), and pre-alloHCT bone marrow blasts ≥5% (HR, 2.76; P = .006) was independently associated with inferior relapse-free survival (RFS), whereas melphalan-based conditioning was associated with superior RFS (HR, 0.52; P = .005). Combining these variables, we constructed a hierarchical model that stratified patients into low-, intermediate-, and high-risk categories with 1-year RFS of 81.3%, 31.3%, and 6.7%, respectively (P < .001). In conclusion, a subset of MN harboring TP53mut who have low blasts pre-alloHCT and received melphalan-based conditioning derived long-term benefit from alloHCT.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3395-3407"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630114","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":"Transplant outcomes using older matched sibling donors compared with young alternative donors: a CIBMTR analysis.","authors":"Karthik Nath, Mei-Jie Zhang, Matthew Bye, Muhammad Bilal Abid, Cara Benjamin, Brian Betts, Neel S Bhatt, Esteban Arrieta Bolaños, Yung-Tsi Bolon, Shahinaz M Gadalla, Michael R Grunwald, Maxwell M Krem, Stephanie J Lee, Steven G E Marsh, Rodrigo Martino, Parinda A Mehta, Filippo Milano, Timothy Prestidge, Jennifer N Saultz, Bronwen E Shaw, Stephen R Spellman, Hannah Choe, Brian C Shaffer","doi":"10.1182/bloodadvances.2024014858","DOIUrl":"10.1182/bloodadvances.2024014858","url":null,"abstract":"<p><strong>Abstract: </strong>Whether older HLA-matched sibling donors (MSD) are preferred over younger alternative donors for allogeneic hematopoietic cell transplantation (allo-HCT) with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis is unclear. We compared outcomes in allo-HCT recipients ≥50 years old after HCT from an older MSD (≥50 years) with recipients of younger (≤35 years) HLA-matched unrelated donor (MUD), haploidentical related donor (haplo), and HLA-mismatched unrelated donor (MMUD), grouped based on PTCy or calcineurin-inhibitor (CNI) based GVHD prophylaxis, that were reported to the Center for International Blood and Marrow Transplant Research between 2014 and 2021. The primary end point was overall survival (OS). Among 14 662 HCT recipients, 3746 received PTCy- and 10 916 CNI-based prophylaxis. In patients receiving PTCy-based HCT, the adjusted 5-year OS was similar between MSD and other donor types: 44% after MSD versus 52% after MUD (multivariable hazard ratio [HR]: 1.20; 95% confidence interval [CI], 1.03-1.41; P = .09), 45% after haplo donor (HR, 1.02; 95% CI, 0.88-1.18; P = 1.00), and 46% after MMUD (HR, 1.00; 95% CI, 0.83-1.21; P = 1.00). Compared with MSD, use of MUD associated with improved disease-free survival (DFS) with PTCy-based (HR, 1.21; 95% CI, 1.05-1.40; P = .048) and CNI-based (HR, 1.09; 95% CI, 1.04-1.15; P < .01) prophylaxis. Haplo donor use associated with worse OS compared with MUD use with PTCy (HR, 1.18; 95% CI, 1.05-1.33; P = .04). Older MSDs result in similar OS compared with younger alternative donors; however, use of a younger MUD associated with improved DFS in older-aged recipients.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3469-3478"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572170","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":"Reassessing the Villalta score's use of signs and symptoms.","authors":"Steven H Yale, Halil Tekiner, Regina Wilson, Eileen S Yale","doi":"10.1182/bloodadvances.2025016750","DOIUrl":"10.1182/bloodadvances.2025016750","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3642-3643"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976741","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":"Beyond FOXO1: AS1842856 inhibits GSK3 to enhance cytotoxic effects in B-ALL.","authors":"Franz Ketzer, Ulrike Büttner, Daniel Geist, Anita Kick, Thomas Wirth, Alexey Ushmorov","doi":"10.1182/bloodadvances.2024015560","DOIUrl":"10.1182/bloodadvances.2024015560","url":null,"abstract":"<p><strong>Abstract: </strong>Activation of the transcription factor forkhead box O1 (FOXO1) contributes to multiple pathological processes. The FOXO1 inhibitor AS1842856 demonstrated strong therapeutic effects in preclinical models of common diseases such as diabetes and anthracycline-induced heart failure. We have previously identified FOXO1 as a B-cell acute lymphoblastic leukemia (B-ALL) dependency and demonstrated in in vivo B-ALL models that AS1842856 increased the survival of animals and decreased B-ALL tumor load in all critical organ compartments, but most efficiently in the central nervous system. Here, we interrogated the underlying molecular mechanisms by comparison of the transcriptomic effects of AS1842856 and Foxo1 knockout (Foxo1-KO) in a B-ALL mouse model. Despite the significant similarity in sets of regulated genes, we identified glycogen synthase kinase (GSK) 3B inhibition as a signature enriched only in AS1842856-treated cells. Using an in vitro kinase assay and an unbiased kinome screen, we identified AS1842856 as a direct GSK3 inhibitor that ultimately stabilizes CTNNB1. CTNNB1-KO partially protected B-ALL cell lines from the cytotoxic effect of AS1842856. At the same time, using a chemical protein degradation model, we found that FOXO1 indeed contributes to the cytotoxic effect of AS1842856. We conclude that AS1842856 targets 2 B-lymphoid vulnerabilities: GSK3 and FOXO1. The unique mode of action, low toxicity, and ability to penetrate the blood-brain barrier warrant further investigation of the therapeutic potential of AS1842856 in B-ALL.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":"9 14","pages":"3441-3454"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599489","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":"Venetoclax-based regimens in octogenarian patients with CLL: efficacy, safety, and comparison to BTKi in a multicenter cohort.","authors":"Andrea Serafin, Alessandro Cellini, Enrica Antonia Martino, Federica Mazzetto, Francesco Angotzi, Anna Maria Frustaci, Monia Marchetti, Riccardo Moia, Alessandro Sanna, Costantino Riemma, Francesca Cibien, Alessandro Noto, Enrico Lista, Myriam Foglietta, Candida Vitale, Vanessa Innao, Martina Bullo, Ester Lovato, Isacco Ferrarini, Costanza Andriola, Laura Ballotta, Idanna Innocenti, Alberto Fresa, Gianmarco Favrin, Marzia Varettoni, Elisa Santambrogio, Lorella Orsucci, Raffaella Pasquale, Massimo Moratti, Luca Laurenti, Marta Coscia, Paolo Sportoletti, Roberto Marasca, Francesca Romana Mauro, Caterina Patti, Enrico Derenzini, Lydia Scarfò, Paolo Ghia, Antonio Cuneo, Alessandra Tedeschi, Livio Trentin, Massimo Gentile, Andrea Visentin","doi":"10.1182/bloodadvances.2025015818","DOIUrl":"10.1182/bloodadvances.2025015818","url":null,"abstract":"<p><strong>Abstract: </strong>Octogenarians represent a significant fraction of patients with chronic lymphocytic leukemia (CLL) but, despite the prevalence of the disease in this age group, limited data are available on the safety and efficacy of novel drugs in this subgroup. We conducted a multicenter retrospective study enrolling 120 octogenarian patients who received venetoclax (Ven) regimens in any line. Regarding efficacy, we found Ven to perform similarly to what is reported in younger patients with CLL, with an overall response rate of 91%, a complete response rate of 44%, and median progression-free survival of 44 months. Concerning safety, we report a toxicity profile that is consistent with previous reports, with most high-grade adverse events being of hematologic or infectious nature, given that 37% and 22% of patients experienced neutropenia or infections of grade 3 or higher. As part of our study, we compared the safety and efficacy data we collected with those obtained in a comparable Bruton tyrosine kinase inhibitor (BTKi)-treated population. We found that these 2 treatments were comparable in terms of overall efficacy, barring a higher rate of complete responses with Ven; safety profiles were different among the 2 groups given that BTKi-treated patients had more cardiovascular toxicities (26% vs 4%) and Ven-treated subjects experienced more infectious events (82% vs 49%). Our data point out that Ven-based regimens are safe and effective in octogenarian patients with CLL despite their higher clinical complexity and comorbidity burden and should provide some basis for the design of prospective studies to further evaluate the optimal treatment regimen in this patient population.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3576-3584"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12275189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964044","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":"Impact of posttransplant cyclophosphamide-based GVHD prophylaxis in patients 70 years and older: an update from BMT CTN 1703.","authors":"Sameem Abedin, Michael J Martens, Javier Bolaños-Meade, Monzr M Al Malki, Qinghua Lian, Lyndsey Runaas, Hany Elmariah, Mahasweta Gooptu, Karilyn T Larkin, Brian C Shaffer, Alison W Loren, Melhem Solh, Amin M Alousi, Omer H Jamy, Miguel-Angel Perales, Andrew Rezvani, Ami Bhatt, Najla El Jurdi, Janny M Yao, Kristy Applegate, Leslie S Kean, Yvonne A Efebera, Ran Reshef, William Clark, Eric Leifer, Wael Saber, Mary M Horowitz, Richard J Jones, Shernan G Holtan, Mehdi Hamadani","doi":"10.1182/bloodadvances.2025015964","DOIUrl":"10.1182/bloodadvances.2025015964","url":null,"abstract":"<p><strong>Abstract: </strong>Allogeneic hematopoietic cell transplant (allo-HCT) is underutilized in adults aged ≥70 years. Morbidity, often driven by graft-versus-host disease (GVHD), is considered a major barrier to its use. The BMT CTN 1703 trial (ClinicalTrials.gov identifier: NCT03959241) randomly assigned adults with hematologic malignancies undergoing allo-HCT after reduced intensity conditioning to receive either posttransplant cyclophosphamide, mycophenolate mofetil, and tacrolimus (PTCy) or tacrolimus and methotrexate (Tac/MTX) for GVHD prophylaxis. Overall study results revealed superior GVHD-free, relapse-free survival (GRFS) with PTCy-based prophylaxis. This analysis explored the impact of PTCy in patients aged ≥70 years enrolled in BMT CTN 1703. We analyzed outcomes for 96 patients aged ≥70 years. PTCy maintained superiority for the primary end point with a GRFS rate of 67.1% compared with 29.5% with Tac/MTX (P = .001). GVHD control and improved immunosuppression-free survival contributed to a lower 1-year nonrelapse mortality (NRM) with PTCy. Furthermore, lower rates of relapse/progression were observed with PTCy, altogether resulting in significantly improved adjusted 1-year survival with PTCy at 94.3% vs 60.2% with Tac/MTX (P = .001). PTCy-based GVHD prophylaxis should be considered standard prophylaxis for older adults. Given low rates of NRM and excellent survival outcomes with this approach, there should be greater consideration for allo-HCT in older patients, particularly patients aged ≥70 years. This trial was registered at www.ClinicalTrials.gov as #NCT03959241.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3495-3501"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062388","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":"Intrathecal chemotherapy for ciltacabtagene autoleucel-associated movement and neurocognitive toxicity.","authors":"Kaitlin Kelly, Jennifer H Cooperrider, Michael R Bishop, Satyajit Kosuri, Andrzej Jakubowiak, Benjamin A Derman","doi":"10.1182/bloodadvances.2024015721","DOIUrl":"10.1182/bloodadvances.2024015721","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3613-3616"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976059","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":"Teclistamab for patients with heavily pretreated relapsed/refractory multiple myeloma and renal impairment.","authors":"Danai Dima, Aimaz Afrough, Utkarsh Goel, Ariel F Grajales-Cruz, Jack Khouri, Kelley Julian, Oren Pasvolsky, Rahul Banerjee, Beatrice Razzo, Christopher J Ferreri, Mariola A Vazquez-Martinez, James A Davis, Aishwarya Sannareddy, Omar Castaneda, Shahzad Raza, Andrew J Portuguese, Mahmoud R Gaballa, Masooma S Rana, Alex Lieberman-Cribbin, Shaun DeJarnette, Rebecca Gonzalez, Anna Chen, Megan M Herr, Lekha Mikkilineni, Hitomi Hosoya, Evguenia Ouchveridze, Gurbakhash Kaur, Adriana Rossi, Leyla Shune, Faiz Anwer, Yi Lin, Shambavi Richard, Douglas W Sborov, Rachid C Baz, Alfred L Garfall, Hans C Lee, Larry D Anderson, Andrew J Cowan, Krina K Patel, Peter M Voorhees, Surbhi Sidana, Doris K Hansen, Shebli Atrash, Sandra P Susanibar-Adaniya","doi":"10.1182/bloodadvances.2025016059","DOIUrl":"10.1182/bloodadvances.2025016059","url":null,"abstract":"<p><strong>Abstract: </strong>Outcomes of bispecific antibodies in patients with renal impairment (RI) are not well characterized, given the exclusion of these patients from clinical trials. Herein, we evaluated patients with relapsed/refractory multiple myeloma and RI treated with standard-of-care teclistamab. RI was defined as creatinine clearance (CrCl) <40 mL/min. CrCl <30 mL/min or dialysis dependence was defined as severe RI. Of the 384 included patients, 81 (21%) had RI, including 45 (18%) with severe RI, and 18 (5%) on dialysis. Patients with RI were more likely to be older (median age, 71 vs 67 years; P = .002) and have a higher median number of previous lines of therapy (7 vs 6; P = .04). Rates and severity of cytokine release syndrome (51% vs 59%; grade ≥3: 1.2% vs 1%) and immune effector cell-associated neurotoxicity syndrome (16% vs 13%; grade ≥3: 2.5% vs 2.6%) were similar in patients with and without RI, respectively. Patients with RI had higher baseline and day 30 post-teclistamab grade ≥3 anemia and grade ≥3 thrombocytopenia. Renal function did not worsen after teclistamab initiation in most patients with RI outside of the context of disease progression. Overall response rate (52% vs 56%; P = .61) and survival outcomes (median progression-free survival, 4.6 vs 6.5 months; P = .62) were comparable in patients with and without RI, respectively, after a median follow-up of 9.9 months. No differences in overall survival or non-relapse mortality were noted. Our findings suggest that treatment with teclistamab is feasible in patients with RI, including those on dialysis, with a similar safety and efficacy profile to patients without RI.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3408-3417"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810606","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":"Belumosudil reduces oral chronic graft-versus-host disease tissue inflammation and fibrosis: a ROCKstar companion study.","authors":"Rubina Sharma, Noa G Holtzman, Iskra Pusic, Corey Cutler, Nathaniel Treister, Rohtesh S Mehta, Amin S Alousi, Nadarajah Vigneswaran, Ayesha Javaid, Francis Boksa, Drashty P Mody, Ana C Costa-da-Silva, Olivier Schueller, Sandrine Macé, Yu Yao, Ran Ji, Beifang Hu, Kathy Marshall, Bruce R Blazar, Stephanie J Lee, Steven Z Pavletic, Jacqueline W Mays","doi":"10.1182/bloodadvances.2025016170","DOIUrl":"10.1182/bloodadvances.2025016170","url":null,"abstract":"<p><strong>Abstract: </strong>Belumosudil (KD025), an oral, selective, Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) inhibitor, is approved for third-line treatment of chronic graft-versus-host disease (cGVHD). Previous studies demonstrated that ROCK2 inhibition reduces blood interleukin-17 (IL-17) activity and promotes regulatory T-cell (Treg cell) recovery. However, these studies did not evaluate immune responses within cGVHD-affected tissues. This study assessed tissue-level immune dynamics in 20 patients with oral cGVHD from the phase 2 ROCKstar trial, before and after 6 months of belumosudil treatment, focusing on key effector sites (oral mucosa [OM], minor salivary glands [MSGs], and skin) and the peripheral blood. After belumosudil treatment, reduction in collagen was observed in OM in parallel with decreased IL-17+ cell frequency in both OM (n = 14 pairs) and MSG (n = 11 pairs). IL-17 was primarily produced by non-T cells in the oral tissues. Immune cell frequencies in the OM decreased after treatment, whereas CD4 Treg cells increased in both the MSG and blood. Per overall or mouth-specific clinical response criteria, responders to belumosudil exhibited a reduction in collagen type I and IL-17 in the OM. Additionally, salivary transforming growth factor β1 (TGF-β1), a critical driver of fibrosis, decreased significantly, with a strong correlation observed between TGF-β1 and IL-17 levels. These findings illustrate the tissue-level response to belumosudil therapy and suggest that there is a reduction in tissue fibrosis and inflammation, thereby highlighting the therapeutic impact of ROCK2 inhibition in mitigating cGVHD. The ROCKstar study was registered at www.ClinicalTrials.gov as #NCT03640481.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3479-3494"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976737","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":"BMP-2 generates a functional bone marrow niche by inducing the differentiation of local mesenchymal cells into CAR cells.","authors":"Ikue Tosa, Mitsuaki Ono, Anh Tuan Dang, Ziyi Wang, Maiko Kimura, Wakana Kitagawa, Kei Ishibashi, Hang Thuy Do, Kun Zhao, Emilio Satoshi Hara, Noboru Asada, Takashi Nagasawa, Toshitaka Oohashi, Naoya Ohara, Takuo Kuboki","doi":"10.1182/bloodadvances.2024014062","DOIUrl":"10.1182/bloodadvances.2024014062","url":null,"abstract":"<p><strong>Abstract: </strong>Ectopic bone marrow (eBM) holds tremendous potential as an artificial organ, serving not only in stem cell transplantation therapies but also as a controlled experimental system for analyzing cellular dynamics and interactions between cells and the matrix during the formation, maintenance, and aging of BM. Although bone morphogenetic protein-2 (BMP-2) has been reported to induce eBM formation, it remains unproven whether BMP-2-induced eBM (BMP-eBM) can provide a functional BM niche that is comparable with native BM in long bones (LB-BM). In this study, through the use of single-cell RNA sequencing and transplantation models, we demonstrate that BMP-eBM displays a microstructure, cellular composition, and functional hematopoiesis similar to LB-BM. BMP-eBM establishes an optimized microenvironment capable of supporting hematopoietic stem cells and CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells, which are critical components of the BM niche. BMP-eBM was able to significantly restore survival in irradiated mice. Through parabiosis and cell transplantation experiments, we identified that in situ adipose tissue-derived CD51highCxcl12-GFP- cells are the principal source of CAR cells within BMP-eBM. Furthermore, BMP-eBM can be isolated and after preconditioning, retransplanted as an independent, functional hematopoietic organ. In conclusion, our study confirms that BMP-eBM functions effectively as a hematopoietic organ, capable of supporting and maintaining a functional BM niche. These findings underscore BMP-2 as a crucial molecule for eBM generation and suggest its potential for addressing BM-related diseases and for use as a platform for in vitro and ex vivo biomedical applications.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":"3598-3612"},"PeriodicalIF":7.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12281123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623607","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}