Mosaic chromosomal alterations (mCAs) in individuals with monoclonal B-cell lymphocytosis (MBL)
Abstract MBL is a precursor condition to chronic lymphocytic leukemia (CLL), characterized by monoclonal B-cells in blood. Mosaic chromosomal alterations (mCAs) are a form of clonal hematopoiesis that include gains, losses, and copy-neutral loss-of-heterozygosity of large DNA segments. Both MBL and...
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Nature Publishing Group
2024-11-01
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| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-024-01175-8 |
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| author | Aswin Sekar Rosalie Griffin Sameer A. Parikh Giulio Genovese Dennis P. Robinson Aaron D. Norman Janet E. Olson Kari G. Rabe Mingma S. Hoel Nicholas J. Boddicker Paul J. Hampel Neil E. Kay James R. Cerhan Esteban Braggio Curtis A. Hanson Celine M. Vachon Tait D. Shanafelt Benjamin L. Ebert Susan L. Slager |
| author_facet | Aswin Sekar Rosalie Griffin Sameer A. Parikh Giulio Genovese Dennis P. Robinson Aaron D. Norman Janet E. Olson Kari G. Rabe Mingma S. Hoel Nicholas J. Boddicker Paul J. Hampel Neil E. Kay James R. Cerhan Esteban Braggio Curtis A. Hanson Celine M. Vachon Tait D. Shanafelt Benjamin L. Ebert Susan L. Slager |
| author_sort | Aswin Sekar |
| collection | DOAJ |
| description | Abstract MBL is a precursor condition to chronic lymphocytic leukemia (CLL), characterized by monoclonal B-cells in blood. Mosaic chromosomal alterations (mCAs) are a form of clonal hematopoiesis that include gains, losses, and copy-neutral loss-of-heterozygosity of large DNA segments. Both MBL and mCAs have been found to increase the risk of CLL and lymphoid malignancies, and the aim of our study was to investigate how mCAs relate to MBL, which is currently unknown. We analyzed genetic, flow cytometric, and hematologic data from 4632 individuals from the Mayo Clinic Biobank and CLL Database. MBL was detected using flow cytometry and classified as high-count (HC) or low-count (LC) MBL based on clone size. mCAs were detected primarily from whole blood DNA using sensitive SNP-array-based analyses. mCAs commonly altered in CLL (deletion of 6q, 11q, 13q, 17p, and trisomy 12) were specific (>99%) to individuals with MBL and CLL. HC-MBL and LC-MBL individuals were 881-fold and 8-fold, respectively, more likely to harbor CLL-associated mCAs than those without MBL. The cell fraction bearing these mCAs typically exceeded the B-cell fraction, suggesting their origin prior to the B-cell lineage. Integrating genetic and blood count data enabled detecting HC-MBL with high specificity in a biobank sample. These results quantify the contribution of mCAs to MBL and could enable large studies of HC-MBL without the need for flow cytometric screening. |
| format | Article |
| id | doaj-art-c4ee9d74bb144a50aa27abf28e99a8eb |
| institution | Kabale University |
| issn | 2044-5385 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj-art-c4ee9d74bb144a50aa27abf28e99a8eb2024-11-10T12:08:41ZengNature Publishing GroupBlood Cancer Journal2044-53852024-11-011411810.1038/s41408-024-01175-8Mosaic chromosomal alterations (mCAs) in individuals with monoclonal B-cell lymphocytosis (MBL)Aswin Sekar0Rosalie Griffin1Sameer A. Parikh2Giulio Genovese3Dennis P. Robinson4Aaron D. Norman5Janet E. Olson6Kari G. Rabe7Mingma S. Hoel8Nicholas J. Boddicker9Paul J. Hampel10Neil E. Kay11James R. Cerhan12Esteban Braggio13Curtis A. Hanson14Celine M. Vachon15Tait D. Shanafelt16Benjamin L. Ebert17Susan L. Slager18Department of Medical Oncology, Dana-Farber Cancer InstituteDivision of Computational Biology, Mayo ClinicDivision of Hematology, Mayo ClinicDepartment of Genetics, Harvard Medical SchoolDivision of Clinical Trials and Biostatistics, Mayo ClinicDivision of Epidemiology, Mayo ClinicDivision of Epidemiology, Mayo ClinicDivision of Clinical Trials and Biostatistics, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Computational Biology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Epidemiology, Mayo ClinicDepartment of Hematology/Oncology, Mayo ClinicDepartment of Laboratory Medicine and Pathology, Division of Hematopathology, Mayo ClinicDivision of Epidemiology, Mayo ClinicDepartment of Medicine, Division of Hematology, Stanford UniversityDepartment of Medical Oncology, Dana-Farber Cancer InstituteDivision of Computational Biology, Mayo ClinicAbstract MBL is a precursor condition to chronic lymphocytic leukemia (CLL), characterized by monoclonal B-cells in blood. Mosaic chromosomal alterations (mCAs) are a form of clonal hematopoiesis that include gains, losses, and copy-neutral loss-of-heterozygosity of large DNA segments. Both MBL and mCAs have been found to increase the risk of CLL and lymphoid malignancies, and the aim of our study was to investigate how mCAs relate to MBL, which is currently unknown. We analyzed genetic, flow cytometric, and hematologic data from 4632 individuals from the Mayo Clinic Biobank and CLL Database. MBL was detected using flow cytometry and classified as high-count (HC) or low-count (LC) MBL based on clone size. mCAs were detected primarily from whole blood DNA using sensitive SNP-array-based analyses. mCAs commonly altered in CLL (deletion of 6q, 11q, 13q, 17p, and trisomy 12) were specific (>99%) to individuals with MBL and CLL. HC-MBL and LC-MBL individuals were 881-fold and 8-fold, respectively, more likely to harbor CLL-associated mCAs than those without MBL. The cell fraction bearing these mCAs typically exceeded the B-cell fraction, suggesting their origin prior to the B-cell lineage. Integrating genetic and blood count data enabled detecting HC-MBL with high specificity in a biobank sample. These results quantify the contribution of mCAs to MBL and could enable large studies of HC-MBL without the need for flow cytometric screening.https://doi.org/10.1038/s41408-024-01175-8 |
| spellingShingle | Aswin Sekar Rosalie Griffin Sameer A. Parikh Giulio Genovese Dennis P. Robinson Aaron D. Norman Janet E. Olson Kari G. Rabe Mingma S. Hoel Nicholas J. Boddicker Paul J. Hampel Neil E. Kay James R. Cerhan Esteban Braggio Curtis A. Hanson Celine M. Vachon Tait D. Shanafelt Benjamin L. Ebert Susan L. Slager Mosaic chromosomal alterations (mCAs) in individuals with monoclonal B-cell lymphocytosis (MBL) Blood Cancer Journal |
| title | Mosaic chromosomal alterations (mCAs) in individuals with monoclonal B-cell lymphocytosis (MBL) |
| title_full | Mosaic chromosomal alterations (mCAs) in individuals with monoclonal B-cell lymphocytosis (MBL) |
| title_fullStr | Mosaic chromosomal alterations (mCAs) in individuals with monoclonal B-cell lymphocytosis (MBL) |
| title_full_unstemmed | Mosaic chromosomal alterations (mCAs) in individuals with monoclonal B-cell lymphocytosis (MBL) |
| title_short | Mosaic chromosomal alterations (mCAs) in individuals with monoclonal B-cell lymphocytosis (MBL) |
| title_sort | mosaic chromosomal alterations mcas in individuals with monoclonal b cell lymphocytosis mbl |
| url | https://doi.org/10.1038/s41408-024-01175-8 |
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