Clonal haematopoiesis and risk of acute myeloid leukemia
Nearly all adults harbor acute myeloid leukemia-related clonal hematopoietic mutations at a variant allele fraction 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 subcohor...
| Main Authors: | , , , |
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| פורמט: | Journal article |
| שפה: | English |
| יצא לאור: |
Ferrata Storti Foundation
2019
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| _version_ | 1826258626439806976 |
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| author | Young, A Tong, R Birmann, B Druley, T |
| author_facet | Young, A Tong, R Birmann, B Druley, T |
| author_sort | Young, A |
| collection | OXFORD |
| description | Nearly all adults harbor acute myeloid leukemia-related clonal hematopoietic mutations at a variant allele fraction 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 acute myeloid leukemia. We identified 35 cases with acute myeloid leukemia 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 acute myeloid leukemia-associated mutations in 97% of all participants (598 mutations, 5.8/person). Individuals with mutations ≥0.01 variant allele fraction had a significantly increased acute myeloid leukemia 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 10 years apart, clonal mutations rarely expanded over time. Our findings are consistent with published evidence that detection of clonal mutations ≥0.01 variant allele fraction identifies individuals at increased risk for acute myeloid leukemia. 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. |
| first_indexed | 2024-03-06T18:36:55Z |
| format | Journal article |
| id | oxford-uuid:0b8e253e-e539-4ee3-83aa-c86c374eb8cd |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:36:55Z |
| publishDate | 2019 |
| publisher | Ferrata Storti Foundation |
| record_format | dspace |
| spelling | oxford-uuid:0b8e253e-e539-4ee3-83aa-c86c374eb8cd2022-03-26T09:30:06ZClonal haematopoiesis and risk of acute myeloid leukemiaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0b8e253e-e539-4ee3-83aa-c86c374eb8cdEnglishSymplectic Elements at OxfordFerrata Storti Foundation2019Young, ATong, RBirmann, BDruley, TNearly all adults harbor acute myeloid leukemia-related clonal hematopoietic mutations at a variant allele fraction 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 acute myeloid leukemia. We identified 35 cases with acute myeloid leukemia 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 acute myeloid leukemia-associated mutations in 97% of all participants (598 mutations, 5.8/person). Individuals with mutations ≥0.01 variant allele fraction had a significantly increased acute myeloid leukemia 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 10 years apart, clonal mutations rarely expanded over time. Our findings are consistent with published evidence that detection of clonal mutations ≥0.01 variant allele fraction identifies individuals at increased risk for acute myeloid leukemia. 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. |
| spellingShingle | Young, A Tong, R Birmann, B Druley, T Clonal haematopoiesis and risk of acute myeloid leukemia |
| title | Clonal haematopoiesis and risk of acute myeloid leukemia |
| title_full | Clonal haematopoiesis and risk of acute myeloid leukemia |
| title_fullStr | Clonal haematopoiesis and risk of acute myeloid leukemia |
| title_full_unstemmed | Clonal haematopoiesis and risk of acute myeloid leukemia |
| title_short | Clonal haematopoiesis and risk of acute myeloid leukemia |
| title_sort | clonal haematopoiesis and risk of acute myeloid leukemia |
| work_keys_str_mv | AT younga clonalhaematopoiesisandriskofacutemyeloidleukemia AT tongr clonalhaematopoiesisandriskofacutemyeloidleukemia AT birmannb clonalhaematopoiesisandriskofacutemyeloidleukemia AT druleyt clonalhaematopoiesisandriskofacutemyeloidleukemia |