Assessment of clonality in T-cell large granular lymphocytic leukemia: flow cytometric T cell receptor Vβ repertoire and T cell receptor gene rearrangement

Abstract

The usefulness of flow cytometric variable β-chain repertoire (FC-Vβ) and T-cell receptor gene rearrangement (TCR-GR) analyses for differentiating T-cell large granular lymphocytic leukemia (T-LGLL) from reactive T-large granular lymphocyte (T-LGL) lymphocytosis has been insufficiently studied to date. In this study, we analyzed the diagnostic value of TCR-GR and FC-Vβ analysis in T-LGLL, and compared these results. In our study, FC-Vβ analysis was positive in all cases of T-LGLL, and clonality assessment of FC-Vβ had equal sensitivity and specificity to GeneScanning analysis but was more sensitive than heteroduplex analysis. Suspected T-cell clonality can best be addressed by evaluating two TCR targets (TCRβ and TCRγ), either in parallel or consecutively. Signal transducer and activator of transcription 3 (STAT3) mutation may provide a diagnostic tool for classifying some cases of T-LGL lymphocytosis as true T-LGLL. Our results further demonstrate a significant correlation of STAT3 mutation with pure red cell aplasia, neutropenia, hepatomegaly, β₂-microglobulin and anemia.

Keywords::

• FC-Vβ
• TCR-GR
• GeneScanning
• heteroduplex
• STAT3
• T-cell large granular lymphocytic leukemia

Acknowledgements

This study was supported by the National Natural Science Foundation of China (Grant Nos. 30871104, 30971296, 81170485, 81170488, 81370656), the Natural Science Foundation of Jiangsu Province (Grant No. BK2010584), Key Projects of Health Department of Jiangsu Province (Grant No. K201108), Jiangsu Province's Medical Elite Program (Grant No. RC2011169), National Public Health Grand Research Foundation (No. 201202017), Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institute (No. JX10231801), Program for Development of Innovative Research Teams in the First Affiliated Hospital of Nanjing Medical University, National Science & Technology Pillar Program (No. 2014BAI09B12) and Project of National Key Clinical Specialty.

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