Michael Linden, M.D., Ph.D.
Associate Professor, Department of Laboratory Medicine and Pathology
Associate Professor, Department of Laboratory Medicine and Pathology
MD, MD, PhD University of Minnesota (Medical Scientist Training Program), 2006
University of Washington, Seattle (Anatomic and Clinical Pathology), 2006-2010
University of Washington, Seattle (Hematopathology), 2010-2011
Saint Mary's University, Winona, MN (Biology), 1998
Awards & Recognition
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 Invited or Peer-Reviewed Lectures
- “Plasma cell neoplasms - a precision diagnostics approach for the practicing pathologist.” American Society for Clinical Pathology Annual Meeting, 2018
- “Flow cytometry of blood and bone marrow: key diagnoses that you never want to miss.” College of American Pathologists Annual Meetings, 2015, 2016, 2017
- “Plasma cell myeloma.” Carlos Alberto Escobedo Seguin Hospital and the Catholic University of Santa Maria Medical School, Arequipa, Peru, 2016.
- “New CAP requirements to standardize flow cytometric MRD testing in myeloma.” Scientific Advisory Board, MRD in Myeloma, Bristol-Myers Squibb, Jersey City, NJ, 2016.
- “New CAP requirements to improve MRD testing standardization.” Advances in MRD Testing in Myeloma Workshop, Multiple Myeloma Research Foundation, New York, NY, 2016.
- “Practical flow cytometry to evaluate lymphoproliferative disorders of marrow” American Society for Clinical Pathology Annual Meeting, 2014 (presented in conjunction with Dr. Kristy Wolniak).
- "Integrated laboratory diagnosis of plasma cell neoplasms – a morphologic, genetic, and flow cytometric approach." American Society of Clinical Pathology national meetings, Boston, MA and Chicago, IL - 2012, 2013
- "Laboratory diagnosis of plasma cell dyscrasias and paraproteinemia associated disorders." Vanderbilt University Medical Center, Department of Pathology, Special Seminar, Nashville, TN - 2011
- "Laboratory diagnosis of plasma cell dyscrasias and paraproteinemia associated disorders." University of California-Davis Department of Pathology and Laboratory Medicine Grand Rounds, Sacramento, CA – 2010
For a more comprehensive list of publications, click HERE.
- 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
- Hassan S, Fanola C, Beckman A, Li F, Nelson AC, Linden M, and Beckman JD. Adult Langerhans histiocytosis with rare BRAF mutation complicated by massive pulmonary embolism [published online ahead of print, 2020 Jul 25]. Thromb Res. 2020;193:207-210. doi:10.1016/j.thromres.2020.07.044
- Vijaya Knight, Thomas Long, Qing H. Meng, Michael A. Linden, and Daniel D. Rhoads. Variability in the laboratory measurement of cytokines: A longitudinal summary of a college of American Pathologists Proficiency Testing Survey. Archives of Pathology & Laboratory Medicine. 2020 May 13. https://doi.org/10.5858/arpa.2019-0519-CP.
- Walton K, Fernandez MR, Sagatys EM, Reff J, Kim J, Lee MC, Kiluk J, Hui JYC, McKenna D, Hupp M, Forster C, Linden MA, Lawrence NJ, Lawrence HR, Pidala J, Pavletic SZ, Blazar BR, Sebti SM, Cleveland JL, Anasetti C, Betts BC. Metabolic reprogramming augments potency of human pSTAT3-inhibited iTregs to suppress alloreactivity. JCI Insight. 2020 Apr 7. pii: 136437. doi: 10.1172/jci.insight.136437.
- Plummer RM, Beckman AK, Hupp MM, Courville EL, Williams SA, and Linden MA. Diagnostic utility of performing flow cytometry on provider-submitted endoscopically collected gastrointestinal samples. OBJD. 2020. 10 (1).doi:10.4236/ojbd.2020.101001
- Cayci Z, Ozturk K, Ustun C, Omer A, Dincer E, Sachs Z, Peterson B, and Linden, M. Sarcoid-like histiocytic proliferations in lymphoma patients can be PET-avid concerning for refractory or recurrent disease. Clinical Lymphoma Myeloma and Leukemia, 2019; 19. doi: 10.1016/j.clml.2019.08.016.
- Gilles SR, Yohe SL, Linden MA, Dolan M, Hirsch B, Grzywacz B. CD161 Is expressed in a subset of T-cell prolymphocytic leukemia cases and Is useful for disease follow-up.Am J Clin Pathol. 2019 Sep 9;152(4):471-478. doi: 10.1093/ajcp/aqz060.
- Courville EL, Yohe S, Shivers P, and Linden MA. VS38 identifies myeloma cells with dim CD38 expression and plasma cells following daratumumab therapy, which interferes with CD38 detection for 4 to 6 months. American Journal of Clinical Pathology, 2 Nov. 2019, https://doi.org/10.1093/ajcp/aqz15
- Lou E, Vogel RI, Hoostal S, Klein M, Linden MA, Teoh D, Geller MA. Tumor-stroma proportion as a predictive biomarker of resistance to platinum-based chemotherapy in patients with ovarian cancer. JAMA Oncol. 2019 Jun 1. doi: 10.1001/jamaoncol.2019.1943.
- Baughn, L. B., and Linden, M. A. Standardization of minimal residual disease testing in multiple myeloma. Journal of Applied Laboratory Medicine. 2017; 2(1); 188-122.
- Baughn, L. B., Sachs, Z., Noble-Orcutt, K. E., Mitra, A., Van Ness, B. G., Linden, M. A. Phenotypic and functional characterization of a bortezomib-resistant multiple myeloma cell line by flow and mass cytometry. Leukemia and Lymphoma. 2017; 58(8):1931-1940.
- McKenna, R. W., Kroft, S., and Linden, M. A. Plasma cell neoplasms. Hematopathology. Jaffee E. S. et al (ed.), Elsevier Saunders, St. Louis, MO, 2016; 2nd edition
- Keeney, M., Halley, J. G., Rhoads, D. D., Ansari, M. Q., Kussick, S. J., Karlon, W. J., Mehta, K. U., Dorfman, D. M., Linden, M. A. Marked variability in reported minimal residual disease lower level of detection of 4 hematolymphoid neoplasms a survey of participants in the College of American Pathologists flow cytometry proficiency testing program. Archives of Pathology and Laboratory Medicine. 2015; 139(10):1276-1280.
- Plasma cell neoplasms: a morphologic, cytogenetic, and immunophenotypic approach, Linden, M. A., and McKenna, R. W., ed., Springer, New York, NY, 2015; 1-152.
- Stessman, H. A. F., Mansoor, A., Linden, M. A., Van Ness, B., Baughn, L. B. Stabilization of activation induced cytidine deaminase by bortezomib does not confer increased drug target mutation frequency. Leukemia and Lymphoma. 2014; 55(1):220-222.
- Fall, D. J., Stessman, H., Patel, S. S., Sachs, Z., Van Ness, B. G., Baughn, L. B., Linden, M. A. Utilization of translational bioinformatics to identify novel biomarkers of bortezomib resistance in multiple myeloma. Journal of Cancer. 2014; 5(9):720-727.
- Stessman, H. A. F., Mansoor, A., Zhan, F., Linden, M. A., Van Ness, B., Baughn, L. B. Bortezomib resistance can be reversed by induced expression of plasma cell maturation markers in a mouse in vitro model of multiple myeloma.. PloS one. 2013; 8(10).
- Stessman, H. A., Mansoor, A., Zhan, F., Janz, S., Linden, M. A., Baughn, L. B., Van Ness, B. Reduced CXCR4 expression is associated with extramedullary disease in a mouse model of myeloma and predicts poor survival in multiple myeloma patients treated with bortezomib. Leukemia. 2013; 27(10):2075-2077.
- Conway, A. B., Kaufman, S. C., Rudrapatna, V. K., Linden, M. A. Crystallizing immunoglobulin presenting as polychromatic crystalline keratopathy: An unusual clinical presentation of monoclonal gammopathy of undetermined significance (MGUS). Laboratory Medicine. 2013; 44(4):344-347.
- Stessman, H. A., Baughn, L. B., Sarver, A., Xia, T., Deshpande, R., Mansoor, A., Walsh, S. A., Sunderland, J. J., Dolloff, N. G., Linden, M. A., Zhan, F., Janz, S., Myers, C. L., Van Ness, B. G. Profiling bortezomib resistance identifies secondary therapies in a mouse myeloma model. Molecular Cancer Therapeutics. 2013; 12(6):1140-1150.
- Linden, M. A., Kirchhof, N., Carlson, C. S., Van Ness, B. G. Targeted overexpression of an activated N-ras gene results in B-cell and plasma cell lymphoproliferation and cooperates with c-myc to induce fatal B-cell neoplasia. Experimental Hematology. 2012; 40(3):216-227.
- Linden, M., Kirchhof, N., Kvitrud, M., Ness, B. V. ABL-MYC retroviral infection elicits bone marrow plasma cell tumors in Bcl-XL transgenic mice. Leukemia Research. 2005; 29(4):435-444.
- Cheung, W. C., Kim, J. S., Linden, M., Peng, L., Van Ness, B., Polakiewicz, R. D., Janz, S. Novel targeted deregulation of c-Myc cooperates with Bcl-XL to cause plasma cell neoplasms in mice. Journal of Clinical Investigation. 2004; 113(12):1763-1773.
- Linden, M., Kirchhof, N., Carlson, C., Van Ness, B. Targeted overexpression of Bcl-XL in B-lymphoid cells results in lymphoproliferative disease and plasma cell malignancies. Blood. 2004; 103(7):2779-2786.
- Croonquist, P. A., Linden, M. A., Zhao, F., Van Ness, B. G. Gene profiling of a myeloma cell line reveals similarities and unique signatures among IL-6 response, N-ras-activating mutations, and co-culture with bone marrow stromal cells. Blood. 2003; 102(7):2581-2592.
American Board of Pathology
- Anatomic and Clinical Pathology
• Lymph node pathology • Bone marrow pathology • Flow cytometry • Minimal residual disease • External quality assurance/proficiency testing • Plasma cell myeloma