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}
Pub Date : 2026-01-22DOI: 10.3324/haematol.2025.288956
Mikkael A Sekeres,Amer M Zeidan,Valeria Santini,Rami S Komrokji,Pierre Fenaux,Michael R Savona,Yazan F Madanat,David Valcárcel,Antoine Regnault,Kristin Creel,Libo Sun,Ying Wan,Shyamala Navada,Tymara Berry,Faye Feller,Uwe Platzbecker,María Díez-Campelo,Esther Natalie Oliva
Red blood cell (RBC) transfusions for anemia associated with lower-risk myelodysplastic syndromes/neoplasms (LR-MDS) often contribute to reduced quality of life (QOL). Thus, reduction in RBC transfusion dependency (TD) is a primary therapeutic goal. Imetelstat is a firstin-class, competitive telomerase inhibitor approved to treat certain adult patients with LR-MDS with RBC-TD anemia who have not responded to, have lost response to, or are ineligible for erythropoiesis-stimulating agents. In the phase III IMerge study (NCT02598661), treatment with imetelstat resulted in clinically meaningful, statistically significant increases in the primary endpoint of ≥8-week RBC transfusion independence (TI) versus placebo. Because patients with LR-MDS experience detrimental effects on numerous facets of QOL (physical, emotional, social, and functional), these exploratory analyses assessed patient-reported outcomes using the Functional Assessment of Chronic Illness Therapy-Fatigue, Quality of Life in Myelodysplasia Scale, and Functional Assessment of Cancer Therapy-Anemia questionnaires as part of the phase III IMerge study. Nominal P values were reported. Fewer imetelstat-treated patients experienced deterioration in fatigue and more imetelstat-treated patients experienced sustained improvement in fatigue and QOL versus placebo. In the imetelstat group, 8-week, 24-week, and 1-year RBC-TI responders had sustained improvements in predefined significance thresholds versus nonresponders for fatigue (70%, 73%, and 88%, respectively, vs. 37%, 41%, and 44%, respectively; P.
{"title":"Imetelstat improves patient-reported outcomes and quality of life in lower-risk myelodysplastic syndromes: results from the phase III IMerge study.","authors":"Mikkael A Sekeres,Amer M Zeidan,Valeria Santini,Rami S Komrokji,Pierre Fenaux,Michael R Savona,Yazan F Madanat,David Valcárcel,Antoine Regnault,Kristin Creel,Libo Sun,Ying Wan,Shyamala Navada,Tymara Berry,Faye Feller,Uwe Platzbecker,María Díez-Campelo,Esther Natalie Oliva","doi":"10.3324/haematol.2025.288956","DOIUrl":"https://doi.org/10.3324/haematol.2025.288956","url":null,"abstract":"Red blood cell (RBC) transfusions for anemia associated with lower-risk myelodysplastic syndromes/neoplasms (LR-MDS) often contribute to reduced quality of life (QOL). Thus, reduction in RBC transfusion dependency (TD) is a primary therapeutic goal. Imetelstat is a firstin-class, competitive telomerase inhibitor approved to treat certain adult patients with LR-MDS with RBC-TD anemia who have not responded to, have lost response to, or are ineligible for erythropoiesis-stimulating agents. In the phase III IMerge study (NCT02598661), treatment with imetelstat resulted in clinically meaningful, statistically significant increases in the primary endpoint of ≥8-week RBC transfusion independence (TI) versus placebo. Because patients with LR-MDS experience detrimental effects on numerous facets of QOL (physical, emotional, social, and functional), these exploratory analyses assessed patient-reported outcomes using the Functional Assessment of Chronic Illness Therapy-Fatigue, Quality of Life in Myelodysplasia Scale, and Functional Assessment of Cancer Therapy-Anemia questionnaires as part of the phase III IMerge study. Nominal P values were reported. Fewer imetelstat-treated patients experienced deterioration in fatigue and more imetelstat-treated patients experienced sustained improvement in fatigue and QOL versus placebo. In the imetelstat group, 8-week, 24-week, and 1-year RBC-TI responders had sustained improvements in predefined significance thresholds versus nonresponders for fatigue (70%, 73%, and 88%, respectively, vs. 37%, 41%, and 44%, respectively; P.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"4 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015412","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":"Abrupt ferritin increases as a marker of cancer in transfusion-dependent thalassemia.","authors":"Elena Chatzikalil,Polyxeni Delaporta,Ilona Binenbaum,Vasiliki Chouliara,Dimitra Kyriakopoulou,Sofirela Berdalli,Konstantinos Bistas,Maria-Ioanna Chatzieleftheriou,Euthalia-Faidra Agiomavriti-Stefanopoulou,Antonis Kattamis","doi":"10.3324/haematol.2025.288434","DOIUrl":"https://doi.org/10.3324/haematol.2025.288434","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"71 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968351","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}
We studied platelet recovery in 93 patients with myelofibrosis, following an allogeneic hemopoietic stem cell transplant (HSCT). The primary end point of the study was achieving a platelet count of 50x10^9/L within day +100, which occurred in 62 patients (67%) and predicted 5 year non relapse mortality (5% vs 55%; p=0.0009) and 5 year actuarial survival (85% vs 38%; p=.
我们研究了93例同种异体造血干细胞移植（HSCT）后骨髓纤维化患者的血小板恢复情况。该研究的主要终点是在100天内达到50x10^9/L的血小板计数，62例患者（67%）实现了这一目标，并预测了5年非复发死亡率（5% vs 55%, p=0.0009）和5年精算生存率（85% vs 38%, p=0.0009）。
{"title":"Platelet recovery delay and survival in patients with myelofibrosis undergoing allogeneic hemopoietic stem cell transplantation.","authors":"Federica Sora',Andrea Bacigalupo,Sabrina Giammarco,Elisabetta Metafuni,Filippo Frioni,Eugenio Galli,Maria Assunta Limongiello,Simona Sica,Patrizia Chiusolo","doi":"10.3324/haematol.2025.288371","DOIUrl":"https://doi.org/10.3324/haematol.2025.288371","url":null,"abstract":"We studied platelet recovery in 93 patients with myelofibrosis, following an allogeneic hemopoietic stem cell transplant (HSCT). The primary end point of the study was achieving a platelet count of 50x10^9/L within day +100, which occurred in 62 patients (67%) and predicted 5 year non relapse mortality (5% vs 55%; p=0.0009) and 5 year actuarial survival (85% vs 38%; p=.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"51 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968699","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 : 2026-01-15DOI: 10.3324/haematol.2025.300189
Martin S Tallman
Not available.
不可用。
{"title":"Don't forget about thrombosis in acute promyelocytic leukemia.","authors":"Martin S Tallman","doi":"10.3324/haematol.2025.300189","DOIUrl":"https://doi.org/10.3324/haematol.2025.300189","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"141 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968695","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 : 2026-01-15DOI: 10.3324/haematol.2025.288700
Mikkel R Simonsen,Toby A Eyre,Eliza A Hawkes,Tarec C El-Galaly
Older patients with lymphoma represent a growing, heterogeneous population whose care is challenged by diverse outcomes, limited evidence, and one-dimensional age definitions. Historically, arbitrary age thresholds such as ≥60 or ≥80 years have guided treatment decisions, yet they fail to capture the biological and functional diversity of aging and can limit opportunities for cure and progress. Current practice relies on arbitrary dose reductions in old age, such as RminiCHOP, despite limited data for optimal intensity and benefit-risk trade-offs. Likewise, novel agents and combination therapies frequently demonstrate discrepant efficacy and safety across age groups, but systematic attempts to optimize dose for the older patients are rarely prioritized. When it comes to clinical trials, documenting benefit of new therapies is more challenging in older patients due to high background mortality that complicates interpretation of overall and progression-free survival and may led to underpowered trials. Moreover, prognostic models developed in younger populations have limited applicability in older patients, as they overlook the broader range of clinically relevant outcomes in older patients, including treatment-related mortality, functional decline, and quality of life. Pre-therapeutic geriatric assessments are prognostic, but their predictive capability remains to be demonstrated in prospective trials before use as treatment decision support tools. Addressing these challenges requires reframing of "old age" to a multidimensional construct, incorporating geriatric assessment, patient preferences, and biological age. More inclusive trial designs, dedicated dose-finding in older patients, and development of holistic, predictive models are critical to advance care. Without this, progress risks stalling for a growing group of our patients.
{"title":"Older patients with lymphoma: navigating a landscape of clinical controversies and barriers to innovation.","authors":"Mikkel R Simonsen,Toby A Eyre,Eliza A Hawkes,Tarec C El-Galaly","doi":"10.3324/haematol.2025.288700","DOIUrl":"https://doi.org/10.3324/haematol.2025.288700","url":null,"abstract":"Older patients with lymphoma represent a growing, heterogeneous population whose care is challenged by diverse outcomes, limited evidence, and one-dimensional age definitions. Historically, arbitrary age thresholds such as ≥60 or ≥80 years have guided treatment decisions, yet they fail to capture the biological and functional diversity of aging and can limit opportunities for cure and progress. Current practice relies on arbitrary dose reductions in old age, such as RminiCHOP, despite limited data for optimal intensity and benefit-risk trade-offs. Likewise, novel agents and combination therapies frequently demonstrate discrepant efficacy and safety across age groups, but systematic attempts to optimize dose for the older patients are rarely prioritized. When it comes to clinical trials, documenting benefit of new therapies is more challenging in older patients due to high background mortality that complicates interpretation of overall and progression-free survival and may led to underpowered trials. Moreover, prognostic models developed in younger populations have limited applicability in older patients, as they overlook the broader range of clinically relevant outcomes in older patients, including treatment-related mortality, functional decline, and quality of life. Pre-therapeutic geriatric assessments are prognostic, but their predictive capability remains to be demonstrated in prospective trials before use as treatment decision support tools. Addressing these challenges requires reframing of \"old age\" to a multidimensional construct, incorporating geriatric assessment, patient preferences, and biological age. More inclusive trial designs, dedicated dose-finding in older patients, and development of holistic, predictive models are critical to advance care. Without this, progress risks stalling for a growing group of our patients.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"101 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968700","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 : 2026-01-15DOI: 10.3324/haematol.2025.288892
Brenna Park-Egan,Catherine L Hough,Patrick G Lyons,Laura F Newell
Not available.
不可用。
{"title":"Performance of commonly used risk triage tools in predicting clinical deterioration among hospitalized hematopoietic stem cell transplant recipients.","authors":"Brenna Park-Egan,Catherine L Hough,Patrick G Lyons,Laura F Newell","doi":"10.3324/haematol.2025.288892","DOIUrl":"https://doi.org/10.3324/haematol.2025.288892","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"30 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968696","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 : 2026-01-15DOI: 10.3324/haematol.2025.288786
Nigel H Russell,Katie D Lewis
Not available.
不可用。
{"title":"All patients with acute myeloid leukemia and FLT3-ITD should be transplanted in first remission. Also in the era of tyrosine kinase inhibitors? - the CON.","authors":"Nigel H Russell,Katie D Lewis","doi":"10.3324/haematol.2025.288786","DOIUrl":"https://doi.org/10.3324/haematol.2025.288786","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"17 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968353","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 : 2026-01-15DOI: 10.3324/haematol.2024.287013
Amy P Hsu, Subrata Paul, Jennifer L Kwan, Philip L F Johnson, Justin Lack, Eva P Szymanski, Jana Lovell, Ladan Foruraghi, Cindy Palmer, Christa S Zerbe, Janine R Daub, Joie Davis, Dennis D Hickstein, Katherine R Calvo, Steven M Holland
GATA2 mutations cause adult-onset bone-marrow failure characterized by cytopenias, infections and increased risk of myeloid malignancy. We reviewed hospital records and referrals of 232 GATA2 mutated individuals from 122 families to gather hematopoietic and syndromic features. Mutations were categorized by GATA2 protein effect: mutation after the 2nd Zinc-finger (Cterm, n=10); missense in the 2nd Zinc-Finger (ZF2, n=104); mutations producing stable truncated protein (Truncation, n=22); Null alleles (mRNA instability, large deletions, n=46); or Enhancer (n=50). Regression models for symptom onset identified earlier onset and increased hazard ratios (HR) between Truncation, Null or ZF2 mutations (13 years, HR 5.00; 17 years, 3.60; 22 years, 2.23 respectively) and Enhancer. Commonly mutated ZF2 amino acids stratified: R396 or T354 presented earlier with increased hazard ratios (16 years, HR 2.96; 19 years, HR 2.16) versus R398 (34 years). Mutation groups with median onset.
{"title":"GATA2 at 14: genotype-phenotype correlations.","authors":"Amy P Hsu, Subrata Paul, Jennifer L Kwan, Philip L F Johnson, Justin Lack, Eva P Szymanski, Jana Lovell, Ladan Foruraghi, Cindy Palmer, Christa S Zerbe, Janine R Daub, Joie Davis, Dennis D Hickstein, Katherine R Calvo, Steven M Holland","doi":"10.3324/haematol.2024.287013","DOIUrl":"https://doi.org/10.3324/haematol.2024.287013","url":null,"abstract":"<p><p>GATA2 mutations cause adult-onset bone-marrow failure characterized by cytopenias, infections and increased risk of myeloid malignancy. We reviewed hospital records and referrals of 232 GATA2 mutated individuals from 122 families to gather hematopoietic and syndromic features. Mutations were categorized by GATA2 protein effect: mutation after the 2nd Zinc-finger (Cterm, n=10); missense in the 2nd Zinc-Finger (ZF2, n=104); mutations producing stable truncated protein (Truncation, n=22); Null alleles (mRNA instability, large deletions, n=46); or Enhancer (n=50). Regression models for symptom onset identified earlier onset and increased hazard ratios (HR) between Truncation, Null or ZF2 mutations (13 years, HR 5.00; 17 years, 3.60; 22 years, 2.23 respectively) and Enhancer. Commonly mutated ZF2 amino acids stratified: R396 or T354 presented earlier with increased hazard ratios (16 years, HR 2.96; 19 years, HR 2.16) versus R398 (34 years). Mutation groups with median onset.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970705","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}
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