TIM3 Is Underexpressed on Myeloblasts in Myelodysplastic Syndrome (MDS)
Kelly J Garner, Stephen P Ten Eyck, Fiona E Craig, Christine G Roth. University of Pittsburgh Medical Center, Pittsburgh, PA
Background: Establishing the diagnosis of MDS may be difficult in cases with other possible contributory factors to morphologic dysplasia (toxic/metabolic factors, post chemotherapy) & requires a multiparametric approach. Flow cytometric studies can be a useful adjunct, especially when focused on the CD34+ myeloblast compartment. Prior studies have found altered levels of antigen expression on MDS myeloblasts as diagnostically useful,but these aberrancies may not be present in all cases. T-cell immunoglobulin mucin-3 (TIM3) is a recently described acute myeloid leukemia (AML) stem cell antigen which has been shown to be overexpressed on leukemic blasts, but has not been well characterized in non-leukemic myeloblasts or MDS. The aim of this study was to evaluate the diagnostic utility of TIM3 flow cytometric expression in separating non-neoplastic and MDS myeloblast populations.
Design: 49 bone marrow & 1 peripheral blood samples were evaluated with the following panel: CD14-FITC,TIM3-PE,CD117-PerCP-Cy5, CD13+CD33-PE-Cy7,CD34-APC,CD3-APC-H7,CD56-V450,CD45-V500. Cases consisted of 22 non-neoplastic cases[15 with a history of cytopenias,no morphologic dysplasia & normal karyotype, & 7 negative staging bone marrows for lymphoma], 9 MDS[1 therapy-related, 1 refractory anemia with ring sideroblasts, 3 refractory cytopenia with multilineage dysplasia, & 4 refractory anemia with excess blasts], & 19 with a history of cytopenias but no evidence of residual AML post chemotherapy. Data was acquired with a FACSCanto-II & analyzed with BD-FACS-DIVA software. TIM3 expression was quantitated as a percentage of the CD34/CD13/33+ myeloblasts as well as myeloblast median fluorescence intensity(MFI). Mann-Whitney U test was used for statistical comparisons.
Results: Lower proportions of TIM3 positive myeloblasts were seen in MDS(median 16.5%, range 4.9-68.4%) as compared to the non-neoplastic cases (median 50.3%, range 26.1-78.1%) & negative post-AML chemotherapy cytopenic cases (median 71.7%, range 33.3-88.3%) (p= 0.012 & 0.0002, respectively). Mean myeloblast TIM3 MFI was also lower in MDS (280, range 103- 650) as compared to the non-neoplastic (455, range 213-826) & negative post-AML chemotherapy cytopenic cases (1032, range 258-3598) (p= 0.011 & 0.0001).
Conclusions: Underexpression of TIM3 is a characteristic feature of myeloblasts in MDS, as compared to non-neoplastic myeloblasts in a variety of clinical settings. Addition of TIM3 to a comprehensive flow cytometric panel focused on evaluating the myeloblast compartment may be a useful diagnostic adjunct. Further studies are required to verify these results & validate for clinical practice.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 237, Wednesday Afternoon