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TIM3 expression by leukemic and non-leukemic myeloblasts.

Christine G Roth1, Kelly Garner, Stephen Ten Eyck

  • 1Department of Pathology, Division of Hematopathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. garciac@upmc.edu

Cytometry. Part B, Clinical Cytometry
|April 5, 2013
PubMed
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T-cell immunoglobulin mucin-3 (TIM3) is expressed on acute myeloid leukemia (AML) cells. However, TIM3 expression is also high in non-leukemic myeloblasts after chemotherapy, limiting its use as a specific AML diagnostic marker.

Area of Science:

  • Hematology
  • Immunology
  • Oncology

Background:

  • T-cell immunoglobulin mucin-3 (TIM3) is an antigen found on acute myeloid leukemia (AML) stem cells.
  • Normal myeloblasts and their comparison to AML myeloblasts require further characterization.
  • A specific flow cytometry marker for distinguishing leukemic from non-neoplastic myeloblasts is diagnostically valuable, particularly post-chemotherapy.

Purpose of the Study:

  • To assess TIM3 expression on myeloblasts in acute myeloid leukemia (AML) and non-neoplastic conditions.
  • To compare TIM3 expression levels between leukemic myeloblasts and normal myeloblasts, including those in a post-chemotherapy setting.
  • To evaluate the diagnostic utility of TIM3 as a specific marker for AML.

Main Methods:

  • Assessed TIM3 myeloblast expression in 69 bone marrow and/or peripheral blood specimens (27 AML, 42 non-neoplastic).

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  • Included 20 non-neoplastic cases with recent chemotherapy history.
  • Evaluated TIM3 median fluorescence intensity (MFI) in myeloblast, monocyte, T cell, and natural killer cell populations.

    • Main Results:

    • TIM3 expression was higher in AML myeloblasts (71.4%) compared to non-neoplastic myeloblasts without chemotherapy history (50.3%).
    • TIM3 expression in post-chemotherapy non-leukemic myeloblasts (72.4%) was similar to AML myeloblasts.
    • Myeloblast TIM3 MFI was elevated in AML and post-chemotherapy non-leukemic myeloblasts compared to non-chemotherapy controls.

    Conclusions:

    • Leukemic myeloblasts overexpress TIM3 compared to non-neoplastic controls.
    • High TIM3 expression is also observed in non-leukemic myeloblasts following chemotherapy.
    • The overlapping expression patterns of TIM3 limit its diagnostic specificity for neoplasia in AML.