Michael Linden

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Credentials

M.D., Ph.D.

Research Summary

Dr. Linden is Director of Hematopathology. As a graduate student, he developed a novel genetically engineered mouse model of multiple myeloma with characteristics similar to those found in human disease. Linden has continued doing research on multiple myeloma and other plasma cell neoplasms while translating that knowledge to clinical application through improved laboratory diagnoses, clinical monitoring, and prediction of disease resistance to therapy.Multiple myeloma is characterized by the proliferation of malignant plasma cells within the bone marrow. Compared to other lymphoid malignancies, the disease has been difficult to study and treat due to its genetic heterogeneity. Investigators use murine and human myeloma cell lines, xenograft models, and genetically engineered mice to identify the multiple genetic pathways involved in the pathobiology of the disease as well as mechanisms of drug resistance. Linden is collaborating with colleagues who are using murine and human cell lines, in addition to primary human samples, to characterize genotypic and immunophenotypic signatures of drug resistance.Linden's laboratory is working to create new diagnostic tests that will aid in predicting chemotherapeutic sensitivity or disease resistance—an individualized therapy approach. In addition, as the analytic sensitivity of flow cytometric methods to evaluate for minimal residual disease is improving, Linden is working with the College of American Pathologists (CAP) to improve and standardize diagnostic testing.In recent years the treatment approach to multiple myeloma has been the subject of a "cure versus control" discussion among clinicians. As novel chemotherapeutic combinations and transplant continue to improve treatment, the likelihood of cure continually increases. Simultaneously, clinical teams have asked for improved diagnostic testing to help define cure. Linden hopes to use his role as a CAP committee chair to guide efforts to improve standardization and quality of flow cytometric testing for myeloma patients.

Selected Publications

For a more comprehensive list of publications, click HERE. 

• Han SY, Mrózek K, Voutsinas J, Wu Q, Morgan EA, Vestergaard H, Ohgami R, Kluin PM, Kristensen TK, Pullarkat S, Møller MB, Schiefer AI, Baughn LB, Kim Y, Czuchlewski D, Hilberink JR, Horny HP, George TI, Dolan M, Ku NK, Arana Yi C, Pullarkat V, Kohlschmidt J, Salhotra A, Soma L, Bloomfield CD, Chen D, Sperr WR, Marcucci G, Cho C, Akin C, Gotlib J, Broesby-Olsen S, Larson M, Linden MA, Deeg HJ, Hoermann G, Perales MA, Hornick JL, Litzow MR, Nakamura R, Weisdorf D, Borthakur G, Huls G, Valent P, Ustun C, Yeung CCS. Secondary cytogenetic abnormalities in core-binding factor AML harboring inv(16) vs t(8;21). Blood Adv. 2021 May 25;5(10):2481-2489. doi: 10.1182/bloodadvances.2020003605.

• Tacker DH, Bashleben C, Long TC, Theel ES, Knight V, Kadkhoda K, Rhoads DD, Linden MA, Fink SL. Inter-laboratory agreement of anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) serologic assays in the expedited College of American Pathologists Proficiency Testing Program. Arch Pathol Lab Med. 2021 Jan 18. doi: 10.5858/arpa.2020-0811-SA.
• Wener MH, Fink A, Bashleben C, Sindelar S, and Linden MA. Long-term variability in immunofluorescence titer of ntibodies to nuclear antigens observed in clinical laboratory proficiency testing surveys. Arch Pathol Lab Med, 2020. doi: https://doi.org/10.5858/arpa.2020-0419-.
• Ustun, C., Morgan, E.A., Ritz, E.M., Vestergaard, H., Pullarkat, S., Kluin, P.M., Ohgami, R., Baughn, L.B., Kim, Y., Ku, N.K., Czuchlewski, D., Boe Møller, M., Schiefer, A.‐I., Mrózek, K., Horny, H.‐P., George, T.I., Kielsgaard Kristensen, T., Beck, T., Nathan, S., Arana Yi, C., Yeung, C., Pullarkat, V., Gotlib, J., Akin, C., Kohlschmidt, J., Salhotra, A., Soma, L., Chen, D., Han, S.Y., Cho, C., Sperr, W., Broesby‐Olsen, S., Linden, M.A., Dolan, M., Hoermann, G., Hornick, J.L., Bloomfield, C., Nakamura, R., Joachim Deeg, H., Litzow, M.R., Borthakur, G., Weisdorf, D., Huls, G., Perales, M.‐A., Valent, P. and Marcucci, G. Core‐binding factor acute myeloid leukemia with inv(16): Older age and high white blood cell count are risk factors for treatment failure. Int J Lab Hematol., 2020. doi:10.1111/ijlh.13338.
• Meghan M. Hupp, Christine Bashleben, Jolene L. Cardinali, David M. Dorfman, William Karlon, Michael Keeney, Catherine Leith, Thomas Long, Claire E. Murphy, Vinodh Pillai, Flavia N. Rosado, Adam C. Seegmiller, Michael A. Linden; Participation in the College of American Pathologists Laboratory Accreditation Program Decreases Variability in B-Lymphoblastic Leukemia and Plasma Cell Myeloma Flow Cytometric Minimal Residual Disease Testing: A Follow-up Survey. Arch Pathol Lab Med, August 2020. doi: https://doi.org/10.5858/arpa.2019-0493-CP

Clinical Summary

• Lymph node pathology • Bone marrow pathology • Flow cytometry • Minimal residual disease • External quality assurance/proficiency testing • Plasma cell myeloma