Distinction of lymphoid and myeloid clonal hematopoiesis.

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

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
11 2021
Historique:
received: 16 02 2021
accepted: 27 08 2021
pubmed: 20 10 2021
medline: 30 12 2021
entrez: 19 10 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1038/s41591-021-01521-4 PMID: 34663986 PMC: PMC8621497
pubmed: 34663986
doi: 10.1038/s41591-021-01521-4
pii: 10.1038/s41591-021-01521-4
pmc: PMC8621497
mid: NIHMS1756847
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1921-1927

Subventions

Organisme : NHLBI NIH HHS
ID : T32 HL094301
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R35 CA253125
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151283
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA206963
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA066996
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA108631
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148050
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R01 HL082945
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148565
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007208
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142711
Pays : United States

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Abhishek Niroula (A)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Laboratory Medicine, Lund University, Lund, Sweden.
ORCID: 0000-0002-5904-0635

Aswin Sekar (A)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Mark A Murakami (MA)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Mark Trinder (M)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Center for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada.

Mridul Agrawal (M)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Waihay J Wong (WJ)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.

Alexander G Bick (AG)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Md Mesbah Uddin (MM)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
ORCID: 0000-0003-1846-0411

Christopher J Gibson (CJ)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
ORCID: 0000-0002-3700-5310

Gabriel K Griffin (GK)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.

Michael C Honigberg (MC)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cardiology Division, Massachusetts General Hospital, Boston, MA, USA.
ORCID: 0000-0001-8630-5021

Seyedeh M Zekavat (SM)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yale University School of Medicine, New Haven, CT, USA.

Kaavya Paruchuri (K)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
Cardiology Division, Massachusetts General Hospital, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.

Pradeep Natarajan (P)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0001-8402-7435

Benjamin L Ebert (BL)

Broad Institute of MIT and Harvard, Cambridge, MA, USA. benjamin_ebert@dfci.harvard.edu.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. benjamin_ebert@dfci.harvard.edu.
Howard Hughes Medical Institute, Bethesda, MD, USA. benjamin_ebert@dfci.harvard.edu.
ORCID: 0000-0003-0197-5451

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Classifications MeSH

questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hémogramme › Distinction of lymphoid and myeloid clonal...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Aberrations des chromosomes › Distinction of lymphoid and myeloid clonal...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiogiques du sang › Hématopoïèse › Hématopoïèse clonale › Distinction of lymphoid and myeloid clonal...
questionsmedicales.fr › Hémopathies et maladies lymphatiques › Hémopathies › Tumeurs hématologiques › Distinction of lymphoid and myeloid clonal...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système hématopoïétique › Cellules de la moelle osseuse › Cellules souches hématopoïétiques › Distinction of lymphoid and myeloid clonal...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Distinction of lymphoid and myeloid clonal...