T-cell immunoglobulin mucin-3 is underexpressed on myeloblasts in untreated myelodysplastic syndrome

Abstract

Establishing the diagnosis of myelodysplastic syndrome (MDS) can be diffi cult and requires a multiparametric approach, with correlation of the clinical, morphologic and genetic features. Although MDS is characterized by dysplastic changes in the myeloid, erythroid or megakaryocytic lineages, some cases may lack overt morphologic dysplasia (i.e. involve less than 10% of cells within a lineage). However, if a MDS-related cytogenetic abnormality is identifi ed, the 2008 World Health Organization criteria permit a MDS diagnosis to be established [1]. In addition, other factors (vitamin/ nutritional defi ciency, toxic/metabolic factors, infections, etc.) can contribute to morphologic dysplasia, complicating the diagnostic interpretation. Detection of a clonal abnormality by cytogenetic studies may be helpful in this clinical context; however, a clonal abnormality is identifi ed in only about half of MDS cases [2].Flow cytometry is an additional ancillary tool that can add value to the diagnostic evaluation [3]. When focused on the CD34 ϩ myeloblast compartment, prior studies have identifi ed altered levels of antigen expression, aberrant expression of lymphoid markers or asynchronous expression of mature myelomonocytic antigens as diagnostically useful [4]. However, these aberrancies may not be present in all cases, necessitating a search for additional markers.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 stem cells (LSCs) as well as most leukemic blasts, but has not been well characterized in non-leukemic myeloblasts or MDS [5]. We evaluated 60 bone marrow and one peripheral blood samples in order to evaluate the diagnostic utility of TIM3 fl ow cytometric expression in separating non-neoplastic and MDS myeloblast populations.Th e study cohort consisted of 17 untreated cases of MDS (four refractory anemia with excess blasts-2, two refractory anemia with excess blasts-1, one MDS-unclassifi able, four refractory cytopenia with multilineage dysplasia, two refractory anemia and four therapy-related MDS), three cases of MDS with ongoing treatment within the last 2 months (with decitabine, azacitidine or induction chemotherapy), 22 non-neoplastic cases (15 with a history of non-MDS related cytopenias, and seven negative staging bone marrows for lymphoma) and 19 negative cases with post-AML chemotherapy with a history of cytopenias but no evidence of residual AML. Most of the cases from the latter two categories also served as controls for a previous study evaluating myeloblast TIM3 expression in AML [6]. TIM3 myeloblast expression was evaluated in a similar manner to that previously reported, using an eight-color fl ow cytometry panel: CD14 -fl uorescein isothiocyanate (FITC), TIM3 -phycoerythrin (PE), CD117 -peridinin -chlorophyll protein complex (PerCP)-Cy5, CD13 ϩ CD33 -PE-Cy7, CD34 -allophycocyanin (APC), CD3 -APC-H7, CD56 -V450, CD45 -V500 [6].Here we report that TIM3 is underexpressed in untreated MDS....