{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T01:17:35Z","timestamp":1778116655989,"version":"3.51.4"},"reference-count":60,"publisher":"American Society of Hematology","issue":"8","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Clonal hematopoiesis of indeterminate potential (CHIP), also referred to as aging-related clonal hematopoiesis, is defined as an asymptomatic clonal expansion of mutant mature hematopoietic cells in \u22654% of blood leukocytes. CHIP associates with advanced age and increased risk for hematological malignancy, cardiovascular disease, and all-cause mortality. Loss-of-function somatic mutations in TET2 are frequent drivers of CHIP. However, the contribution of aging-associated cooperating cell-extrinsic drivers, like inflammation, remains underexplored. Using bone marrow (BM) transplantation and newly developed genetic mosaicism (HSC-SCL-Cre-ERT; Tet2+\/flox; R26+\/tm6[CAG-ZsGreen1]Hze) mouse models of Tet2+\/\u2212driven CHIP, we observed an association between increased Tet2+\/\u2212 clonal expansion and higher BM levels of the inflammatory cytokine interleukin-1 (IL-1) upon aging. Administration of IL-1 to mice carrying CHIP led to an IL-1 receptor 1 (IL-1R1)\u2013dependent expansion of Tet2+\/\u2212 hematopoietic stem and progenitor cells (HSPCs) and mature blood cells. This expansion was caused by increased Tet2+\/\u2212 HSPC cell cycle progression, increased multilineage differentiation, and higher repopulation capacity compared with their wild-type counterparts. In agreement, IL-1\u03b1\u2013treated Tet2+\/\u2212 hematopoietic stem cells showed increased DNA replication and repair transcriptomic signatures and reduced susceptibility to IL-1\u03b1\u2013mediated downregulation of self-renewal genes. More important, genetic deletion of IL-1R1 in Tet2+\/\u2212 HPSCs or pharmacologic inhibition of IL-1 signaling impaired Tet2+\/\u2212 clonal expansion, establishing the IL-1 pathway as a relevant and therapeutically targetable driver of Tet2+\/\u2212 CHIP progression during aging.<\/jats:p>","DOI":"10.1182\/blood.2022016835","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T21:35:27Z","timestamp":1668548127000},"page":"886-903","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":143,"title":["Aging drives <i>Tet2<\/i>\n                  <i>+\/\u2212<\/i> clonal hematopoiesis via IL-1 signaling"],"prefix":"10.1182","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4096-4448","authenticated-orcid":false,"given":"Francisco","family":"Caiado","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Comprehensive Cancer Center Zurich, Zurich, Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0342-3127","authenticated-orcid":false,"given":"Larisa V.","family":"Kovtonyuk","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Comprehensive Cancer Center Zurich, Zurich, Switzerland"}]},{"given":"Nagihan G.","family":"Gonullu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Comprehensive Cancer Center Zurich, Zurich, Switzerland"}]},{"given":"Jonas","family":"Fullin","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Comprehensive Cancer Center Zurich, Zurich, Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-0957","authenticated-orcid":false,"given":"Steffen","family":"Boettcher","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Comprehensive Cancer Center Zurich, Zurich, Switzerland"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4676-7931","authenticated-orcid":false,"given":"Markus G.","family":"Manz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Comprehensive Cancer Center Zurich, Zurich, Switzerland"}]}],"member":"234","reference":[{"issue":"26","key":"2023092918001688600_bib1","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1056\/NEJMoa1409405","article-title":"Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence","volume":"371","author":"Genovese","year":"2014","journal-title":"N\u00a0Engl J 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