Distinction of lymphoid and myeloid clonal hematopoiesis

Nat Med. 2021 Nov;27(11):1921-1927. doi: 10.1038/s41591-021-01521-4. Epub 2021 Oct 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Cell Count
  • Chromosome Aberrations
  • Clonal Hematopoiesis / genetics*
  • Clonal Hematopoiesis / physiology*
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / pathology*
  • Hematopoietic Stem Cells / cytology*
  • Humans