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Niroula A, Sekar A, Murakami MA, Trinder M, Agrawal M, Wong WJ, Bick AG, Uddin MM, Gibson CJ, Griffin GK, Honigberg MC, Zekavat SM, Paruchuri K, Natarajan P, Ebert BL
Nat. Med. 27 (11) 1921-1927 [2021-11-00; online 2021-10-18]
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.
PubMed 34663986
DOI 10.1038/s41591-021-01521-4
Crossref 10.1038/s41591-021-01521-4
mid: NIHMS1756847
pmc: PMC8621497
pii: 10.1038/s41591-021-01521-4