Back to Authors

Timm, Michael M

Mayo Clinic

From the Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, Rochester, MN.

Citations 13

Single Antibody Detection of T‐Cell Receptor αβ Clonality by Flow Cytometry Rapidly Identifies Mature T‐Cell Neoplasms and Monotypic Small CD8‐Positive Subsets of Uncertain Significance
Jevremović, Dragan , Otteson, Gregory E., Timm, Michael, Olteanu, Horatiu , Timm, Michael M, Olteanu, Horatiu , Horna, Pedro , Jevremovic, Dragan , Shi, Min

Cytometry Part B: Clinical Cytometry | April 12, 2019 | Volume: 98 | Issue: 1 | Pages: 99-107

10.1002/cyto.b.21782 Get It

BackgroundThe diagnosis of T‐cell neoplasms is often challenging, due to overlapping features with reactive T‐cells and limitations of currently available T‐cell clonality assays. The description of an antibody specific for one of two mutually exclusive T‐cell receptor (TCR) β‐chain constant regions (TRBC1) provide an opportunity to facilitate the detection of clonal TCRαβ T‐cells based on TRBC‐restriction.MethodsTwenty patients with mature T‐cell neoplasms and 44 patients without evidence of T‐cell neoplasia were studied. Peripheral blood (51), bone marrow (10), and lymph node (3) specimens were evaluated by 9‐color flow cytometry including TRBC1 (CD2/CD3/CD4/CD5/CD7/CD8/CD45/TCRγδ/TRBC1 and/or CD2/CD3/CD4/CD5/CD7/CD8/CD26/CD45/TRBC1). Monophasic TRBC1 expression on any immunophenotypically distinct CD4‐positive or CD8‐positive/TCRγδ‐negative T‐cell subset was considered indicative of clonality.ResultsMonophasic (clonal) TRBC1 expression was identified on immunophenotypically abnormal T‐cells from all 20 patients with T‐cell malignancies (100% sensitivity), including 17 cases with either >97% or <3% TRBC1‐positive events, and three cases with monophasic homogenous TRBC1‐dim expression. All immunophenotypically distinct CD4‐positive and CD8‐positive/TCRγδ‐negative T‐cell subsets from 44 patients without T‐cell malignancies showed the expected mixture of TRBC1‐positive and TRBC‐1‐negative subpopulations (non‐clonal), except for seven patients (16%) with very small CD8‐positive T‐cell subsets exhibiting a monophasic (clonal) pattern.ConclusionInclusion of a single anti‐TRBC1 antibody into a diagnostic T‐cell flow cytometry panel facilitates the rapid identification of T‐cell neoplasms, in addition to small monotypic CD8‐positive subsets of uncertain significance. © 2019 International Clinical Cytometry Society
The prognostic significance of polyclonal bone marrow plasma cells in patients with relapsing multiple myeloma
Ghosh, Toshi, Gonsalves, Wilson I. , Jevremović, Dragan , Dingli, David , Timm, Michael, Morice, William G. , Kapoor, Prashant , Kourelis, Taxiarchis , Lacy, Martha Q. , Hayman, Suzanne R. , Lin, Yi , Russell, Stephen J. , Lust, John A., Zeldenrust, Steven R., Warsame, Rahma , Hwa, Yi L. , Kyle, Robert A. , Kumar, Shaji , Timm, Michael M, Kourelis, Taxiarchis V, Buadi, Francis K. , Leung, Nelson , Go, Ronald S , Warsame, Rahma , Dispenzieri, Angela , Morice, William George , Leung, Nelson , Go, Ronald S. , Gertz, Morie A. , Rajkumar, S. Vincent , Gonsalves, Wilson , Russell, Stephen J , Jevremovic, Dragan , Dingli, David , Lin, Yi

American Journal of Hematology | June 1, 2017 | Volume: 92 | Issue: 9 | Pages: No page available

10.1002/ajh.24807 Get It

AbstractPrior studies have revealed that the presence of increasing number of polyclonal plasma cells (pPCs) in the bone marrow (BM) are associated with better outcomes in newly diagnosed multiple myeloma (MM) patients. This effect has not been studied in patients with MM at the time of disease relapse. We determined the prognostic value of depletion of pPCs in the BM by 7‐color multiparameter flow cytometry in a series of 174 relapsing MM patients. The time to next therapy (TTNT) in those with <5% pPCs was 9.4 months versus 13.9 months in those with ≥5% pPCs (P = .0091). The median overall survival (OS) in those with <5% pPCs was 21.4 months, while the median OS was not reached in those patients with ≥5% pPCs (P = .019). Of the 109 patients with standard risk cytogenetics, the median OS of those with <5% pPCs was 28.4 months, while the median OS was not reached in those with ≥5% pPCs (P = .033). As such, <5% pPCs in the BM appears to have prognostic utility in identifying a subset of relapsing MM patients, even with standard‐risk cytogenetics, who have a particularly adverse outcome.
Loss of Blast Heterogeneity in Myelodysplastic Syndrome and Other Chronic Myeloid Neoplasms
Jevremović, Dragan , Timm, Michael, Reichard, Kaaren K. , Morice, William G. , Hanson, Curtis A. , Viswanatha, David S., Howard, Matthew T., Nguyen, Phuong L., Timm, Michael M, Morice, William George , Jevremovic, Dragan

American Journal of Clinical Pathology | August 14, 2014 | Volume: 142 | Issue: 3 | Pages: 292-298

10.1309/ajcp73qsllydegxk Get It

Abstract Objectives: Flow cytometry immunophenotyping has been suggested as an adjunctive technique in the evaluation of myeloid malignancies, especially in the myelodysplastic syndromes. However, its use has been limited due to complexity and cost restraints. The goal of this study is to attempt a simpler approach to flow cytometry immunophenotyping in myeloid neoplasms. Methods: We analyzed bone marrow specimens of 45 selected patients and an additional 99 consecutive random patients using a limited antibody panel. Results: Normal CD34-positive blasts show a characteristic pattern of CD13/HLA-DR expression, with three readily identifiable subpopulations. In contrast, myeloid neoplasms frequently show loss of this heterogeneity. Conclusions: Analysis of a limited antibody panel with a focus on CD13/HLA-DR expression provides relatively high specificity and sensitivity for the detection of myeloid neoplasms.