Clonal hematopoiesis and risk of acute myeloid leukemia.
Haematologica
; 104(12): 2410-2417, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31004019
ABSTRACT
Nearly all adults harbor acute myeloid leukemia (AML)-related clonal hematopoietic mutations at a variant allele fraction (VAF) of ≥0.0001, yet relatively few develop hematologic malignancies. We conducted a nested analysis in the Nurses' Health Study and Health Professionals Follow-Up Study blood subcohorts, with up to 22 years of follow up to investigate associations of clonal mutations of ≥0.0001 allele frequency with future risk of AML. We identified 35 cases with AML that had pre-diagnosis peripheral blood samples and matched two controls without history of cancer per case by sex, age, and ethnicity. We conducted blinded error-corrected sequencing on all study samples and assessed variant-associated risk using conditional logistic regression. We detected AML-associated mutations in 97% of all participants (598 mutations, 5.8/person). Individuals with mutations ≥0.01 variant allele fraction had a significantly increased AML risk (OR 5.4, 95%CI 1.8-16.6), as did individuals with higher-frequency clones and those with DNMT3A R882H/C mutations. The risk of lower-frequency clones was less clear. In the 11 case-control sets with samples banked ten years apart, clonal mutations rarely expanded over time. Our findings are consistent with published evidence that detection of clonal mutations ≥0.01 VAF identifies individuals at increased risk for AML. Further study of larger populations, mutations co-occurring within the same pre-leukemic clone and other risk factors (lifestyle, epigenetics, etc.), are still needed to fully elucidate the risk conferred by low-frequency clonal hematopoiesis in asymptomatic adults.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
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Biomarcadores Tumorais
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Células Clonais
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Evolução Clonal
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Hematopoese
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Mutação
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article