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Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia

BACKGROUND: Previous population health studies examining adults with acute myeloid leukemia (AML); however many of these, such as the Cancer Genome Atlas, are derived from databases collected by large urban centers. Due to its unique industry and environmental exposures, we hypothesized the West Vir...

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Autores principales: Shultz, Carl, Gates, Christopher, Petros, William, Ross, Kelly, Veltri, Laruen, Craig, Michael, Wen, Sijin, Primerano, Donald A., Hazlehurst, Lori, Denvir, James, Sdrimas, Konstantinos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10026309/
https://www.ncbi.nlm.nih.gov/pubmed/36382570
http://dx.doi.org/10.1002/cnr2.1746
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author Shultz, Carl
Gates, Christopher
Petros, William
Ross, Kelly
Veltri, Laruen
Craig, Michael
Wen, Sijin
Primerano, Donald A.
Hazlehurst, Lori
Denvir, James
Sdrimas, Konstantinos
author_facet Shultz, Carl
Gates, Christopher
Petros, William
Ross, Kelly
Veltri, Laruen
Craig, Michael
Wen, Sijin
Primerano, Donald A.
Hazlehurst, Lori
Denvir, James
Sdrimas, Konstantinos
author_sort Shultz, Carl
collection PubMed
description BACKGROUND: Previous population health studies examining adults with acute myeloid leukemia (AML); however many of these, such as the Cancer Genome Atlas, are derived from databases collected by large urban centers. Due to its unique industry and environmental exposures, we hypothesized the West Virginia Appalachian population may have different mutational trends and clinical outcomes. AIMS: To address the concern of under‐representation of rural minorities in cancer genomic databases, we performed exploratory whole exome sequencing in patients with newly diagnosed AML in rural Appalachia. METHODS & RESULTS: Correlations between genetic variants and clinical outcome variables were examined via retrospective chart review. A total of 26 patients were identified and whole exome sequencing was performed. Median age was 68 years old. Twenty‐one patients had de novo AML (84%). As per European LeukemiaNet (ELN) criteria, 8 patients were favorable (32%), 12 were intermediate (48%), and 5 were adverse risk (20%). Eight patients proceeded to transplant. The median progression‐free survival and overall survival were 16.5 months and 26.6 months, respectively. We noted an increased tumor mutation burden and a higher frequency of specific known driver mutations when compared to The Cancer Genome Atlas database; we also found novel mutations in MUC3A, MUC5AC, HCAR3, ORT2B, and PABPC. Survival outcomes were slightly lower than national average and BCOR mutation correlated with inferior outcomes. CONCLUSION: Our findings provide novel insight into detrimental mutations in AML in a rural, underrepresented population. We discovered several novel mutations and higher frequency of some known driver mutations, which will help us identify therapeutic targets to improve patient outcomes.
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spelling pubmed-100263092023-03-21 Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia Shultz, Carl Gates, Christopher Petros, William Ross, Kelly Veltri, Laruen Craig, Michael Wen, Sijin Primerano, Donald A. Hazlehurst, Lori Denvir, James Sdrimas, Konstantinos Cancer Rep (Hoboken) Original Articles BACKGROUND: Previous population health studies examining adults with acute myeloid leukemia (AML); however many of these, such as the Cancer Genome Atlas, are derived from databases collected by large urban centers. Due to its unique industry and environmental exposures, we hypothesized the West Virginia Appalachian population may have different mutational trends and clinical outcomes. AIMS: To address the concern of under‐representation of rural minorities in cancer genomic databases, we performed exploratory whole exome sequencing in patients with newly diagnosed AML in rural Appalachia. METHODS & RESULTS: Correlations between genetic variants and clinical outcome variables were examined via retrospective chart review. A total of 26 patients were identified and whole exome sequencing was performed. Median age was 68 years old. Twenty‐one patients had de novo AML (84%). As per European LeukemiaNet (ELN) criteria, 8 patients were favorable (32%), 12 were intermediate (48%), and 5 were adverse risk (20%). Eight patients proceeded to transplant. The median progression‐free survival and overall survival were 16.5 months and 26.6 months, respectively. We noted an increased tumor mutation burden and a higher frequency of specific known driver mutations when compared to The Cancer Genome Atlas database; we also found novel mutations in MUC3A, MUC5AC, HCAR3, ORT2B, and PABPC. Survival outcomes were slightly lower than national average and BCOR mutation correlated with inferior outcomes. CONCLUSION: Our findings provide novel insight into detrimental mutations in AML in a rural, underrepresented population. We discovered several novel mutations and higher frequency of some known driver mutations, which will help us identify therapeutic targets to improve patient outcomes. John Wiley and Sons Inc. 2022-11-16 /pmc/articles/PMC10026309/ /pubmed/36382570 http://dx.doi.org/10.1002/cnr2.1746 Text en © 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Shultz, Carl
Gates, Christopher
Petros, William
Ross, Kelly
Veltri, Laruen
Craig, Michael
Wen, Sijin
Primerano, Donald A.
Hazlehurst, Lori
Denvir, James
Sdrimas, Konstantinos
Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia
title Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia
title_full Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia
title_fullStr Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia
title_full_unstemmed Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia
title_short Association of genetic variants and survival in patients with acute myeloid leukemia in rural Appalachia
title_sort association of genetic variants and survival in patients with acute myeloid leukemia in rural appalachia
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10026309/
https://www.ncbi.nlm.nih.gov/pubmed/36382570
http://dx.doi.org/10.1002/cnr2.1746
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