Hematopoietic stem cells (HSCs) are critical for lifelong blood cell generation. After mutation accumulation and functional disruption, HSCs may transform into leukemic stem cells (LSCs), leading to malignant hematological disorders. However, both HSCs and LSCs are highly heterogeneous, which hinders our comprehensive understanding of their biological characteristics and clinical application. Here, we identified multimerin 1 (Mmrn1) as a reliable marker for the most primitive HSCs and LSCs. We found that Mmrn1 was abundantly present in human and mouse HSCs. Interestingly, HSCs with high levels of Mmrn1 displayed increased quiescence and regenerative capacity, accompanied by megakaryocytic lineage commitment. Importantly, Mmrn1 deficiency gradually impairs HSC self-renewal under stress of transplantation due to reduced quiescence. Additionally, we noticed that Mmrn1 was specifically upregulated in acute myeloid leukemia (AML) cells, and its overexpression predicted poor patient prognosis. Further investigation revealed that Mmrn1 marked a subset of quiescent LSCs responsible for AML initiation and development, and that deletion of Mmrn1 delays AML progression. Collectively, these data broaden our knowledge of stem cell heterogeneity in the context of normal and malignant hematopoiesis and advance the precision diagnosis and therapy of AML in the clinic.
{"title":"Mmrn1 expression defines a novel subset of hematopoietic stem cells and leukemia stem cells with great self-renewal potential.","authors":"Naicheng Chen,Lijing Yang,Fang Chen,Hao Zeng,Xiaoyi Zhong,Yanying Liu,Zijin Chen,Mengying Yao,Yukai Lu,Mingqiang Shen,Mo Chen,Yang Xu,Song Wang,Xi Zhang,Junping Wang,Mengjia Hu","doi":"10.3324/haematol.2025.287609","DOIUrl":"https://doi.org/10.3324/haematol.2025.287609","url":null,"abstract":"Hematopoietic stem cells (HSCs) are critical for lifelong blood cell generation. After mutation accumulation and functional disruption, HSCs may transform into leukemic stem cells (LSCs), leading to malignant hematological disorders. However, both HSCs and LSCs are highly heterogeneous, which hinders our comprehensive understanding of their biological characteristics and clinical application. Here, we identified multimerin 1 (Mmrn1) as a reliable marker for the most primitive HSCs and LSCs. We found that Mmrn1 was abundantly present in human and mouse HSCs. Interestingly, HSCs with high levels of Mmrn1 displayed increased quiescence and regenerative capacity, accompanied by megakaryocytic lineage commitment. Importantly, Mmrn1 deficiency gradually impairs HSC self-renewal under stress of transplantation due to reduced quiescence. Additionally, we noticed that Mmrn1 was specifically upregulated in acute myeloid leukemia (AML) cells, and its overexpression predicted poor patient prognosis. Further investigation revealed that Mmrn1 marked a subset of quiescent LSCs responsible for AML initiation and development, and that deletion of Mmrn1 delays AML progression. Collectively, these data broaden our knowledge of stem cell heterogeneity in the context of normal and malignant hematopoiesis and advance the precision diagnosis and therapy of AML in the clinic.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"222 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015418","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}
Pub Date : 2026-01-22DOI: 10.3324/haematol.2025.300390
Jessica Hochberg, Mitchell S Cairo
Not available.
不可用。
{"title":"Comment on: Severe toxicity and poor efficacy of reinduction chemotherapy are associated with overall poor outcomes in relapsed B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group AALL1331 trial.","authors":"Jessica Hochberg, Mitchell S Cairo","doi":"10.3324/haematol.2025.300390","DOIUrl":"https://doi.org/10.3324/haematol.2025.300390","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018302","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}
Pub Date : 2026-01-22DOI: 10.3324/haematol.2025.289266
Pedro Asensi Cantò,Juan Montoro,Aitana Balaguer-Roselló,Marta Villalba,Pedro Chorão,Alberto Louro,Pablo Granados,Juan Eirís,Ana Bataller,Inés Gómez-Seguí,Pilar Solves,Guillermo León,Brais Lamas,Lara Eritzpokhoff,Nalle Vallejo,Ana Hervás,Mercedes Hurtado,Javier López,Miguel Mansilla-Polo,Juan P Reig,Marta García Gamón Valero,Marta De la Rubia,Carla Satorres,Javier De la Rubia,Miguel A Sanz,Jaime Sanz
Chronic graft-versus-host disease (cGVHD) remains a leading cause of late morbidity after allogeneic hematopoietic cell transplantation (HCT), but its phenotype under modern prophylaxis with post-transplant cyclophosphamide (PTCy) is not well characterized. We conducted a prospective, single-center study of 600 consecutive adults undergoing HCT with PTCy-based prophylaxis to assess incidence, clinical manifestations, treatment response, prognostic factors, and outcomes. Donors included matched siblings (36%), matched unrelated (34%), haploidentical (24%), and mismatched unrelated (6%). The 1-year cumulative incidence of moderate-to-severe cGVHD was 22% (95% CI, 19-26%). The mouth was the most frequently involved organ (64%), with lichen planus-like changes as the predominant diagnostic feature, whereas sclerotic forms were uncommon. Notably, 27% of moderate-to-severe cases were managed successfully without systemic corticosteroids. The cumulative incidence of systemic therapy requirement was 15% at 1 year, with risk significantly higher in donors ≥30 years and in female-to-male transplants. Among 105 patients requiring systemic steroids, 64% achieved complete response, 32% discontinued immunosuppression, yet 18% developed cGVHD-related sequelae. Mouth ulcers and erythema, as well as a lung score ≥2 at steroid initiation independently predicted shorter failure-free survival. At 2 years, overall survival, cGVHD-free relapse-free survival, and GVHD-free relapse-free survival were 76% (95% CI, 72-79), 63% (95% CI, 60-68), and 57% (95% CI, 53-62), respectively. In conclusion, after HCT with PTCy-based prophylaxis, systemic therapy was required in only a minority of patients, with risk influenced by donor age and sex mismatch rather than donor type. While corticosteroids were generally effective, a substantial subset required salvage therapy, underscoring the burden of refractory cGVHD and the need for steroid-sparing approaches and novel interventions.
{"title":"Chronic graft-versus-host disease in the era of post-transplant cyclophosphamide.","authors":"Pedro Asensi Cantò,Juan Montoro,Aitana Balaguer-Roselló,Marta Villalba,Pedro Chorão,Alberto Louro,Pablo Granados,Juan Eirís,Ana Bataller,Inés Gómez-Seguí,Pilar Solves,Guillermo León,Brais Lamas,Lara Eritzpokhoff,Nalle Vallejo,Ana Hervás,Mercedes Hurtado,Javier López,Miguel Mansilla-Polo,Juan P Reig,Marta García Gamón Valero,Marta De la Rubia,Carla Satorres,Javier De la Rubia,Miguel A Sanz,Jaime Sanz","doi":"10.3324/haematol.2025.289266","DOIUrl":"https://doi.org/10.3324/haematol.2025.289266","url":null,"abstract":"Chronic graft-versus-host disease (cGVHD) remains a leading cause of late morbidity after allogeneic hematopoietic cell transplantation (HCT), but its phenotype under modern prophylaxis with post-transplant cyclophosphamide (PTCy) is not well characterized. We conducted a prospective, single-center study of 600 consecutive adults undergoing HCT with PTCy-based prophylaxis to assess incidence, clinical manifestations, treatment response, prognostic factors, and outcomes. Donors included matched siblings (36%), matched unrelated (34%), haploidentical (24%), and mismatched unrelated (6%). The 1-year cumulative incidence of moderate-to-severe cGVHD was 22% (95% CI, 19-26%). The mouth was the most frequently involved organ (64%), with lichen planus-like changes as the predominant diagnostic feature, whereas sclerotic forms were uncommon. Notably, 27% of moderate-to-severe cases were managed successfully without systemic corticosteroids. The cumulative incidence of systemic therapy requirement was 15% at 1 year, with risk significantly higher in donors ≥30 years and in female-to-male transplants. Among 105 patients requiring systemic steroids, 64% achieved complete response, 32% discontinued immunosuppression, yet 18% developed cGVHD-related sequelae. Mouth ulcers and erythema, as well as a lung score ≥2 at steroid initiation independently predicted shorter failure-free survival. At 2 years, overall survival, cGVHD-free relapse-free survival, and GVHD-free relapse-free survival were 76% (95% CI, 72-79), 63% (95% CI, 60-68), and 57% (95% CI, 53-62), respectively. In conclusion, after HCT with PTCy-based prophylaxis, systemic therapy was required in only a minority of patients, with risk influenced by donor age and sex mismatch rather than donor type. While corticosteroids were generally effective, a substantial subset required salvage therapy, underscoring the burden of refractory cGVHD and the need for steroid-sparing approaches and novel interventions.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"20 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015406","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}
Pub Date : 2026-01-22DOI: 10.3324/haematol.2025.288274
Ashley N Chavana,Emily J Mason,John P Woodhouse,Olga A Taylor,Monica M Gramatges,Joanna S Yi,Sandi Pruitt,Brooke M Bernhardt,Kathleen Ludwig,Laura Klesse,Kenneth Heym,Timothy Griffin,Marley Roberts,Rodrigo Erana,Juan Carlos Bernini,Hong Zhu,Philip J Lupo,Karen R Rabin,Michael E Scheurer,Steven D Mittelman,Van Huynh,Etan Orgel,Austin L Brown
Not available.
不可用。
{"title":"Incidence and outcomes of treatment-associated hepatotoxicity during pediatric acute lymphoblastic leukemia induction therapy: a Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium report.","authors":"Ashley N Chavana,Emily J Mason,John P Woodhouse,Olga A Taylor,Monica M Gramatges,Joanna S Yi,Sandi Pruitt,Brooke M Bernhardt,Kathleen Ludwig,Laura Klesse,Kenneth Heym,Timothy Griffin,Marley Roberts,Rodrigo Erana,Juan Carlos Bernini,Hong Zhu,Philip J Lupo,Karen R Rabin,Michael E Scheurer,Steven D Mittelman,Van Huynh,Etan Orgel,Austin L Brown","doi":"10.3324/haematol.2025.288274","DOIUrl":"https://doi.org/10.3324/haematol.2025.288274","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"52 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015410","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}
Pub Date : 2026-01-22DOI: 10.3324/haematol.2025.300285
Alex Bataller,Ghayas C Issa
Not available.
不可用。
{"title":"Menin and BCL2 inhibitors- shaken and stirred.","authors":"Alex Bataller,Ghayas C Issa","doi":"10.3324/haematol.2025.300285","DOIUrl":"https://doi.org/10.3324/haematol.2025.300285","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"7 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015413","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":"Functional impact of a deep intronic variant in the RPS19 gene detected in a case of Diamond-Blackfan anemia syndrome.","authors":"Rika Kanezaki,Tsutomu Toki,Ryo Okuse,Akie Kobayashi,Moeka Sato,Sayaka Kimura,Ko Kudo,Tomohiko Sato,Tatsuhiko Tanaka,Kenichi Yoshida,Yosuke Kawai,Katsushi Tokunaga,Junko Takita,Seishi Ogawa,Kiminori Terui,Etsuro Ito","doi":"10.3324/haematol.2025.300131","DOIUrl":"https://doi.org/10.3324/haematol.2025.300131","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"101 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015414","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}
Pub Date : 2026-01-22DOI: 10.3324/haematol.2025.300405
Howard Oster,Moshe Mittelman
Not available.
不可用。
{"title":"Rethinking the effectiveness of hypomethylating agents in myelodysplastic syndromes: the 50%-2-year wall.","authors":"Howard Oster,Moshe Mittelman","doi":"10.3324/haematol.2025.300405","DOIUrl":"https://doi.org/10.3324/haematol.2025.300405","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"7 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015407","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}
Characterized by somatic mutations (e.g., DNMT3A) in blood cells, clonal hematopoiesis (CH) is an age-related process wherein mutated hematopoietic stem and progenitor cells (HSPCs) expand. This expansion thereby increases the risk of all-cause mortality, myeloid hematologic malignancies and other nonmalignant disorders, yet the risk factors that contribute to CH are still largely unknown. Periodontitis induces low-grade systemic inflammation and affects an estimated 62% of dentate adults globally, which may influence CH-associated pathologies. Periodontitis was modeled by bilateral maxillary second molar ligation in mice; CH was established using hematopoietic-specific Dnmt3a R878H mutant mice. Periodontal bone destruction was assessed via micro-computed tomography and H/E-staining. Changes in bone marrow HSPCs, peripheral blood cells, and gingival immune cells were analyzed by flow cytometry. Key molecular mediators were identified through transcriptomic sequencing of sorted gingival myeloid cells and serum cytokine arrays. Results showed that ligature-induced periodontitis (LIP) promoted Dnmt3a R878H-driven clonal hematopoiesis, manifested as a myeloid-biased phenotype characterized by increased myeloid cells in the gingiva and peripheral blood. The selective enrichment of the Dnmt3a R878H clones during LIP is primarily because Dnmt3a R878H HSCs exhibit enhanced resistance and maintain competitive advantages within inflammatory microenvironments. Transcriptomic analysis revealed upregulation of Ccl17 in gingival R878H myeloid cells, which was corroborated by elevated serum and bone marrow levels of CCL17. The CCL17 upregulation drove myeloid cells recruitment to the gingiva, exacerbating periodontitis while simultaneously reinforcing Dnmt3a R878H HSC expansion. This study highlights the necessity of controlling local chronic inflammation, such as periodontitis, in the clinical management of CH.
{"title":"Ligature-induced periodontitis promotes Dnmt3a R878H-driven clonal hematopoiesis.","authors":"Qiao Yuan,Min Liao,Ziyao Zhuang,Chenyan Huang,Rixin Chen,Yuxian Song,Yu Wu,Peihui Zou,Lili Li,Hua Nie,Miaomiao Zhang,Shiyuan Song,Yanfen Li,Fuhua Yan","doi":"10.3324/haematol.2025.288827","DOIUrl":"https://doi.org/10.3324/haematol.2025.288827","url":null,"abstract":"Characterized by somatic mutations (e.g., DNMT3A) in blood cells, clonal hematopoiesis (CH) is an age-related process wherein mutated hematopoietic stem and progenitor cells (HSPCs) expand. This expansion thereby increases the risk of all-cause mortality, myeloid hematologic malignancies and other nonmalignant disorders, yet the risk factors that contribute to CH are still largely unknown. Periodontitis induces low-grade systemic inflammation and affects an estimated 62% of dentate adults globally, which may influence CH-associated pathologies. Periodontitis was modeled by bilateral maxillary second molar ligation in mice; CH was established using hematopoietic-specific Dnmt3a R878H mutant mice. Periodontal bone destruction was assessed via micro-computed tomography and H/E-staining. Changes in bone marrow HSPCs, peripheral blood cells, and gingival immune cells were analyzed by flow cytometry. Key molecular mediators were identified through transcriptomic sequencing of sorted gingival myeloid cells and serum cytokine arrays. Results showed that ligature-induced periodontitis (LIP) promoted Dnmt3a R878H-driven clonal hematopoiesis, manifested as a myeloid-biased phenotype characterized by increased myeloid cells in the gingiva and peripheral blood. The selective enrichment of the Dnmt3a R878H clones during LIP is primarily because Dnmt3a R878H HSCs exhibit enhanced resistance and maintain competitive advantages within inflammatory microenvironments. Transcriptomic analysis revealed upregulation of Ccl17 in gingival R878H myeloid cells, which was corroborated by elevated serum and bone marrow levels of CCL17. The CCL17 upregulation drove myeloid cells recruitment to the gingiva, exacerbating periodontitis while simultaneously reinforcing Dnmt3a R878H HSC expansion. This study highlights the necessity of controlling local chronic inflammation, such as periodontitis, in the clinical management of CH.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"101 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015408","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：