MSACL 2019 US Abstract

Development of an LC-MS/MS Method for Assessment of Mutant Isocitrate Dehydrogenase (mIDH) Cancer Biomarkers in Acute Myeloid Leukemia

Jeffrey D. Whitman (1), Pauline Proum (1), Derek Galligan (2), Gabriel Mannis (2), Sonam Prakash (1), Kara L. Lynch (1)
(1) Department of Laboratory Medicine, University of California, San Francisco, (2) Department of Hematology/Oncology, University of California, San Francisco

Warning: Undefined variable $headshot in /var/www/html/view_abstract/view_abstract_in_program.php on line 704

Jeffrey Whitman (Presenter) University of California, San Francisco

Presenter Bio: Jeffrey Whitman is a Clinical Pathology Resident at the University of California, San Francisco (UCSF). He holds an M.S. in biochemistry and molecular biology from University of California, Riverside and M.D. from the David Geffen School of Medicine at UCLA. His introduction to medicine began in the clinical laboratory of his local county hospital and carried on with him into medical school, which ultimately influenced his choice in residency. At UCSF his current research pursuits involve translational mass spectrometry in toxicology and metabolomics under Zuckerberg San Francisco General Hospital Clinical Chemistry Faculty, Kara Lynch and Alan Wu. His professional interests revolve around closing the gap of diagnostic disparities in underserved and global health settings.

Relevant Financial Disclosures (within past 24 months) No relevant financial relationship(s) to disclose. Discussing Products? NO, presenter will NOT present educational content related to products/services of the ineligible company(ies) listed above. Conflict mitigation NOT REQUIRED.

Mutant IDH (mIDH) cancers produce a neomorphic oncometabolite called 2-hydroxyglutarate, which induces epigenetic DNA hypermethylation associated with tumorigenesis. Recent FDA approval of small molecule mIDH inhibitors in acute myeloid leukemia (AML) has created a need for functional assays to measure 2-HG and genome-wide epigenetic methylation for diagnostic, prognostic, and drug efficacy studies. We developed and validated a quantitative LC-MS/MS assay to measure 2-HG and epigenetic markers in peripheral blood and bone marrow for assessment of mIDH AML cases. Our findings in a limited number of bone marrow DNA extracts from 6 mIDH AML patients show two cases of significant hypermethylation upon presentation and relapse, respectively. Further studies will be necessary to evaluate the clinical utility of these biomarkers in mIDH neoplasms.