Genomic characterization of chronic lymphocytic leukemia in patients of African ancestry
Abstract Despite the considerable effort to characterize the genomic landscape of chronic lymphocytic leukemia (CLL), published data have been almost exclusively derived from patients of European Ancestry (EA), with significant underrepresentation of minorities, including patients of African Ancestr...
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| Format: | Article |
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Nature Publishing Group
2025-02-01
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| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-024-01207-3 |
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| author | Cecilia Bonolo de Campos Chantal E. McCabe Laura A. Bruins Daniel R. O’Brien Sochilt Brown Renee C. Tschumper Cristine Allmer Yuan Xiao Zhu Kari G. Rabe Sameer A. Parikh Neil E. Kay Huihuang Yan James R. Cerhan John N. Allan Richard R. Furman J. Brice Weinberg Danielle M. Brander Diane F. Jelinek Marta Chesi Susan L. Slager Esteban Braggio |
| author_facet | Cecilia Bonolo de Campos Chantal E. McCabe Laura A. Bruins Daniel R. O’Brien Sochilt Brown Renee C. Tschumper Cristine Allmer Yuan Xiao Zhu Kari G. Rabe Sameer A. Parikh Neil E. Kay Huihuang Yan James R. Cerhan John N. Allan Richard R. Furman J. Brice Weinberg Danielle M. Brander Diane F. Jelinek Marta Chesi Susan L. Slager Esteban Braggio |
| author_sort | Cecilia Bonolo de Campos |
| collection | DOAJ |
| description | Abstract Despite the considerable effort to characterize the genomic landscape of chronic lymphocytic leukemia (CLL), published data have been almost exclusively derived from patients of European Ancestry (EA), with significant underrepresentation of minorities, including patients of African Ancestry (AA). To begin to address this gap, we evaluated whether differences exist in the genetic and transcriptomic features of 157 AA and 440 EA individuals diagnosed with CLL. We sequenced 59 putative driver genes and found an increased frequency of high-impact mutations in AA CLL, including genes of the DNA damage repair (DDR) pathway. Telomere erosion was also increased in AA CLL, amplifying the notion of increased genomic instability in AA CLL. Furthermore, we found transcription enrichment of the Tumor Necrosis Factor-alpha (TNFα) Signaling via NF-κB pathway in AA CLL compared to EA CLL, suggesting that tumor promoting inflammation plays an important role in AA CLL. In summary, these results suggest that genomic instability and NF-kB activation is more prevalent in AA CLL than EA CLL. |
| format | Article |
| id | doaj-art-4bfee96a080a4291b3a40579dd4bdf38 |
| institution | Kabale University |
| issn | 2044-5385 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj-art-4bfee96a080a4291b3a40579dd4bdf382025-02-09T12:13:04ZengNature Publishing GroupBlood Cancer Journal2044-53852025-02-011511810.1038/s41408-024-01207-3Genomic characterization of chronic lymphocytic leukemia in patients of African ancestryCecilia Bonolo de Campos0Chantal E. McCabe1Laura A. Bruins2Daniel R. O’Brien3Sochilt Brown4Renee C. Tschumper5Cristine Allmer6Yuan Xiao Zhu7Kari G. Rabe8Sameer A. Parikh9Neil E. Kay10Huihuang Yan11James R. Cerhan12John N. Allan13Richard R. Furman14J. Brice Weinberg15Danielle M. Brander16Diane F. Jelinek17Marta Chesi18Susan L. Slager19Esteban Braggio20Division of Hematology/Oncology, Mayo ClinicDivision of Computational Biology, Mayo ClinicDivision of Hematology/Oncology, Mayo ClinicDivision of Computational Biology, Mayo ClinicDivision of Hematology/Oncology, Mayo ClinicDepartment of Immunology, Mayo ClinicDivision of Clinical Trials and Biostatistics, Mayo ClinicDivision of Hematology/Oncology, Mayo ClinicDivision of Clinical Trials and Biostatistics, Mayo ClinicDivision of Hematology, Mayo ClinicDepartment of Immunology, Mayo ClinicDivision of Computational Biology, Mayo ClinicDivision of Epidemiology, Mayo ClinicDivision of Hematology and Medical Oncology, Weill Cornell Medical CollegeDivision of Hematology and Medical Oncology, Weill Cornell Medical CollegeDivisions of Hematology and Hematologic Malignancies & Cellular Therapy & VA Medical CenterDivision of Hematologic Malignancy and Cellular Therapy, Duke Cancer InstituteDepartment of Immunology, Mayo ClinicDivision of Hematology/Oncology, Mayo ClinicDivision of Computational Biology, Mayo ClinicDivision of Hematology/Oncology, Mayo ClinicAbstract Despite the considerable effort to characterize the genomic landscape of chronic lymphocytic leukemia (CLL), published data have been almost exclusively derived from patients of European Ancestry (EA), with significant underrepresentation of minorities, including patients of African Ancestry (AA). To begin to address this gap, we evaluated whether differences exist in the genetic and transcriptomic features of 157 AA and 440 EA individuals diagnosed with CLL. We sequenced 59 putative driver genes and found an increased frequency of high-impact mutations in AA CLL, including genes of the DNA damage repair (DDR) pathway. Telomere erosion was also increased in AA CLL, amplifying the notion of increased genomic instability in AA CLL. Furthermore, we found transcription enrichment of the Tumor Necrosis Factor-alpha (TNFα) Signaling via NF-κB pathway in AA CLL compared to EA CLL, suggesting that tumor promoting inflammation plays an important role in AA CLL. In summary, these results suggest that genomic instability and NF-kB activation is more prevalent in AA CLL than EA CLL.https://doi.org/10.1038/s41408-024-01207-3 |
| spellingShingle | Cecilia Bonolo de Campos Chantal E. McCabe Laura A. Bruins Daniel R. O’Brien Sochilt Brown Renee C. Tschumper Cristine Allmer Yuan Xiao Zhu Kari G. Rabe Sameer A. Parikh Neil E. Kay Huihuang Yan James R. Cerhan John N. Allan Richard R. Furman J. Brice Weinberg Danielle M. Brander Diane F. Jelinek Marta Chesi Susan L. Slager Esteban Braggio Genomic characterization of chronic lymphocytic leukemia in patients of African ancestry Blood Cancer Journal |
| title | Genomic characterization of chronic lymphocytic leukemia in patients of African ancestry |
| title_full | Genomic characterization of chronic lymphocytic leukemia in patients of African ancestry |
| title_fullStr | Genomic characterization of chronic lymphocytic leukemia in patients of African ancestry |
| title_full_unstemmed | Genomic characterization of chronic lymphocytic leukemia in patients of African ancestry |
| title_short | Genomic characterization of chronic lymphocytic leukemia in patients of African ancestry |
| title_sort | genomic characterization of chronic lymphocytic leukemia in patients of african ancestry |
| url | https://doi.org/10.1038/s41408-024-01207-3 |
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