Title | Paired bone marrow and peripheral blood samples demonstrate lack of widespread dissemination of some CH clones. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Osman AEG, Mencia-Trinchant N, Saygin C, Moma L, Kim A, Housman G, Pozsgai M, Sinha E, Chandra P, Hassane DC, Sboner A, Sangani K, DiNardi N, Johnson C, Wallace SS, Jabri B, Luu H, Guzman ML, Desai P, Godley LA |
Journal | Blood Adv |
Volume | 7 |
Issue | 9 |
Pagination | 1910-1914 |
Date Published | 2023 May 09 |
ISSN | 2473-9537 |
Keywords | Bone Marrow, Clonal Hematopoiesis, Clone Cells, Hematopoiesis, Hematopoietic Stem Cells, Humans |
Abstract | Clonal hematopoiesis (CH) represents clonal expansion of mutated hematopoietic stem cells detectable in the peripheral blood or bone marrow through next generation sequencing. The current prevailing model posits that CH mutations detected in the peripheral blood mirror bone marrow mutations with clones widely disseminated across hematopoietic compartments. We sought to test the hypothesis that all clones are disseminated throughout hematopoietic tissues by comparing CH in hip vs peripheral blood specimens collected at the time of hip replacement surgery. Here, we show that patients with osteoarthritis have a high prevalence of CH, which involve genes encoding epigenetic modifiers and DNA damage repair pathway proteins. Importantly, we illustrate that CH, including clones with variant allele frequencies >10%, can be confined to specific bone marrow spaces and may be eliminated through surgical excision. Future work will define whether clones with somatic mutations in particular genes or clonal fractions of certain sizes are either more likely to be localized or are slower to disseminate into the peripheral blood and other bony sites. |
DOI | 10.1182/bloodadvances.2022008521 |
Alternate Journal | Blood Adv |
PubMed ID | 36453641 |
PubMed Central ID | PMC10172868 |
Grant List | T32 GM007281 / GM / NIGMS NIH HHS / United States R01 CA248747 / CA / NCI NIH HHS / United States R21 AG066552 / AG / NIA NIH HHS / United States |
Related Faculty:
Andrea Sboner, Ph.D.