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Distinction of lymphoid and myeloid clonal hematopoiesis

Niroula, Abhishek LU ; Sekar, Aswin ; Murakami, Mark A. ; Trinder, Mark ; Agrawal, Mridul ; Wong, Waihay J. ; Bick, Alexander G. ; Uddin, Md Mesbah ; Gibson, Christopher J. and Griffin, Gabriel K. , et al. (2021) In Nature Medicine 27(11). p.1921-1927
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Medicine
volume
27
issue
11
pages
1921 - 1927
publisher
Nature Publishing Group
external identifiers
  • pmid:34663986
  • scopus:85117257521
ISSN
1078-8956
DOI
10.1038/s41591-021-01521-4
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
id
79ebc715-db23-4446-95e7-3604661df0db
date added to LUP
2021-11-05 14:41:44
date last changed
2025-03-11 01:19:27
@article{79ebc715-db23-4446-95e7-3604661df0db,
  abstract     = {{<p>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.</p>}},
  author       = {{Niroula, Abhishek and Sekar, Aswin and Murakami, Mark A. and Trinder, Mark and Agrawal, Mridul and Wong, Waihay J. and Bick, Alexander G. and Uddin, Md Mesbah and Gibson, Christopher J. and Griffin, Gabriel K. and Honigberg, Michael C. and Zekavat, Seyedeh M. and Paruchuri, Kaavya and Natarajan, Pradeep and Ebert, Benjamin L.}},
  issn         = {{1078-8956}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1921--1927}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Distinction of lymphoid and myeloid clonal hematopoiesis}},
  url          = {{http://dx.doi.org/10.1038/s41591-021-01521-4}},
  doi          = {{10.1038/s41591-021-01521-4}},
  volume       = {{27}},
  year         = {{2021}},
}