Pharmacogenomic Analyses Implicate B Cell Developmental Status and

CD20 (MS4A1) MKL1 (MRTFA) TGFB1 obinutuzumab (Gazyva®) ofatumumab (Arzerra®, Kesimpta®) rituximab (Rituxan®)

Journal

Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052

Informations de publication

Date de publication:
07 06 2023
Historique:
received: 03 04 2023
revised: 02 06 2023
accepted: 04 06 2023
medline: 29 6 2023
pubmed: 28 6 2023
entrez: 28 6 2023
Statut: epublish

Résumé

Monoclonal antibody (mAb) therapy directed against CD20 is an important tool in the treatment of B cell disorders. However, variable patient response and acquired resistance remain important clinical challenges. To identify genetic factors that may influence sensitivity to treatment, the cytotoxic activity of three CD20 mAbs: rituximab; ofatumumab; and obinutuzumab, were screened in high-throughput assays using 680 ethnically diverse lymphoblastoid cell lines (LCLs) followed by a pharmacogenomic assessment. GWAS analysis identified several novel gene candidates. The most significant SNP, rs58600101, in the gene

Identifiants

pubmed: 37371044
pii: cells12121574
doi: 10.3390/cells12121574
pmc: PMC10297299
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Antigens, CD20 0
Antineoplastic Agents 0
Prednisolone 9PHQ9Y1OLM

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIH HHS
ID : 1UM2AI30836-01
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016086
Pays : United States

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Auteurs

George W Small (GW)

Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Farida S Akhtari (FS)

Biostatistics and Computational Biology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.

Adrian J Green (AJ)

Department of Biological Sciences, Bioinformatics Research Center, North Carolina State University, Raleigh, NC 27695, USA.

Tammy M Havener (TM)

Structural Genomics Consortium and Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Michael Sikes (M)

Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, USA.

Julia Quintanhila (J)

Clinical Development, Foundation Medicine, Boston, MA 02141, USA.

Ricardo D Gonzalez (RD)

Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

David M Reif (DM)

Predictive Toxicology Branch, Division of Translational Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.

Alison A Motsinger-Reif (AA)

Biostatistics and Computational Biology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.

Howard L McLeod (HL)

Center for Precision Medicine and Functional Genomics, Utah Tech University, 225 South University Ave, St. George, UT 84770, USA.

Tim Wiltshire (T)

Pharmacotherapy and Experimental Therapeutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Center for Pharmacogenomics and Individualized Therapy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

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