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<p>Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are two types of clonal hematopoiesis (CH) associated with hematological parameters and malignancy risk. Here we show, in genomic data from 546,090 biobank participants, that co-occurring CH (≥2 CH mutations detected) is present in 1.6% of cancer-free individuals and shows strong evidence for selection (up to 804x enrichment). Co-occurrence is more frequent in those with a prior cancer (3.6%), suggesting treatment-induced selection. Acquisition of CHIP usually precedes mCAs with co-occurrences manifesting stronger phenotypic disruptions in telomere attrition and hematologic parameters than component CH events. Individuals with co-occurring CH have pronounced elevations in risk of myeloid and lymphoid malignancies (HRs&gt;40), particularly when CHIP and mCAs overlap genomically. Our findings indicate CH co-occurrences are selected for in the aging population and identify CH clones with notable implications for future malignancy risk.</p>

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Co-occurring clonal hematopoiesis exhibits strong selection and high leukemia risk

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月21日

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  • Kara M. Barnao,
  • Aubrey K. Hubbard,
  • Irenaeus C. C. Chan,
  • Weiyin Zhou,
  • Yasminka A. Jakubek,
  • Giulio Genovese,
  • Wendy S. W. Wong,
  • Rebecca L. Kelly,
  • Corey D. Young,
  • Derek W. Brown,
  • Wen-Yi Huang,
  • Neal D. Freedman,
  • Kristine Jones,
  • Amy Hutchinson,
  • Belynda Hicks,
  • Duc Tran,
  • Donna Arnett,
  • Kathleen C. Barnes,
  • Joshua C. Bis,
  • Eric Boerwinkle,
  • Jennifer A. Brody,
  • April P. Carson,
  • Daniel I. Chasman,
  • Michael H. Cho,
  • Pinkal Desai,
  • Margaret F. Doyle,
  • Myriam Fornage,
  • Xiuqing Guo,
  • Nancy Heard-Costa,
  • Marguerite Ryan Irvin,
  • Andrew D. Johnson,
  • Sharon L. R. Kardia,
  • Charles Kooperberg,
  • Daniel Levy,
  • Joshua P. Lewis,
  • Yun Li,
  • Ruth J. F. Loos,
  • Taralynn M. Mack,
  • Rasika A. Mathias,
  • Braxton D. Mitchell,
  • Kari E. North,
  • Nathan Pankratz,
  • Patricia A. Peyser,
  • Michael H. Preuss,
  • Bruce M. Psaty,
  • Laura M. Raffield,
  • Susan Redline,
  • Stephen S. Rich,
  • Jerome I. Rotter,
  • Edwin K. Silverman,
  • Albert V. Smith,
  • Jennifer A. Smith,
  • Adrienne Stilp,
  • Yin Cao,
  • Paul Scheet,
  • Alexander P. Reiner,
  • Alexander G. Bick,
  • Stephen J. Chanock,
  • Paul L. Auer,
  • Kelly L. Bolton,
  • Mitchell J. Machiela

摘要

Clonal hematopoiesis of indeterminate potential (CHIP) and mosaic chromosomal alterations (mCAs) are two types of clonal hematopoiesis (CH) associated with hematological parameters and malignancy risk. Here we show, in genomic data from 546,090 biobank participants, that co-occurring CH (≥2 CH mutations detected) is present in 1.6% of cancer-free individuals and shows strong evidence for selection (up to 804x enrichment). Co-occurrence is more frequent in those with a prior cancer (3.6%), suggesting treatment-induced selection. Acquisition of CHIP usually precedes mCAs with co-occurrences manifesting stronger phenotypic disruptions in telomere attrition and hematologic parameters than component CH events. Individuals with co-occurring CH have pronounced elevations in risk of myeloid and lymphoid malignancies (HRs>40), particularly when CHIP and mCAs overlap genomically. Our findings indicate CH co-occurrences are selected for in the aging population and identify CH clones with notable implications for future malignancy risk.