Distinction of lymphoid and myeloid clonal hematopoiesis

Niroula, AbhishekLund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Broad Institute,Dana-Farber Cancer Institute (author)

Clonal hematopoiesis (CH) results from somatic genomic alterations that drive clonal expansion of blood cells. Somatic gene mutations associated with hematologic malignancies detected in hematopoietic cells of healthy individuals, referred to as CH of indeterminate potential (CHIP), have been associated with myeloid malignancies, while mosaic chromosomal alterations (mCAs) have been associated with lymphoid malignancies. Here, we analyzed CHIP in 55,383 individuals and autosomal mCAs in 420,969 individuals with no history of hematologic malignancies in the UK Biobank and Mass General Brigham Biobank. We distinguished myeloid and lymphoid somatic gene mutations, as well as myeloid and lymphoid mCAs, and found both to be associated with risk of lineage-specific hematologic malignancies. Further, we performed an integrated analysis of somatic alterations with peripheral blood count parameters to stratify the risk of incident myeloid and lymphoid malignancies. These genetic alterations can be readily detected in clinical sequencing panels and used with blood count parameters to identify individuals at high risk of developing hematologic malignancies.

Sekar, AswinDana-Farber Cancer Institute (author)
Murakami, Mark A.Dana-Farber Cancer Institute (author)
Trinder, MarkBroad Institute,University of British Columbia (author)
Agrawal, MridulDana-Farber Cancer Institute (author)
Wong, Waihay J.Broad Institute (author)
Bick, Alexander G.Vanderbilt University,Broad Institute (author)
Uddin, Md MesbahBroad Institute,Massachusetts General Hospital (author)
Gibson, Christopher J.Broad Institute,Dana-Farber Cancer Institute (author)
Griffin, Gabriel K.Broad Institute (author)
Honigberg, Michael C.Broad Institute,Massachusetts General Hospital (author)
Zekavat, Seyedeh M.Broad Institute,Yale University (author)
Paruchuri, KaavyaBroad Institute,Harvard Medical School,Massachusetts General Hospital (author)
Natarajan, PradeepHarvard Medical School,Massachusetts General Hospital,Broad Institute (author)
Ebert, Benjamin L.Dana-Farber Cancer Institute,Howard Hughes Medical Institute,Broad Institute (author)
HematogenomicsForskargrupper vid Lunds universitet (creator_code:org_t)

In:Nature Medicine: Springer Science and Business Media LLC27:11, s. 1921-19271078-89561546-170X

By the author/editor: Niroula, Abhishe ...; Sekar, Aswin; Murakami, Mark A ...; Trinder, Mark; Agrawal, Mridul; Wong, Waihay J.; show more...; Bick, Alexander ...; Uddin, Md Mesbah; Gibson, Christop ...; Griffin, Gabriel ...; Honigberg, Micha ...; Zekavat, Seyedeh ...; Paruchuri, Kaavy ...; Natarajan, Prade ...; Ebert, Benjamin ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Hematology

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