High Incidence of Clonal CD8+ T-cell Proliferation in Non-malignant Conditions May Reduce the Significance of T-cell Clonality Assay for Differential Diagnosis in Oncohematology

Abstract

Polymerase chain reaction (PCR) analysis of rearranged T-cell receptor (TCR) genes is a valuable diagnostic tool for differential diagnosis of T-cell large granular lymphocytic (T-LGL) leukemia and reactive lymphocytosis. Age-related narrowing of T-cells repertoire and expansion of immune or autoimmune clones may lead to false-positive results. The objective of this study was to evaluate the specificity and positive predictive value of PCR-based clonality assessment for a differential diagnostics of T-LGL leukemia. Rearrangements of TCRG and TCRB genes using the BIOMED-2 protocol were assessed in healthy individuals including the elderly (n = 62) and patients with rheumatic diseases (n = 14), transitory reactive CD8+ lymphocytosis (n = 17), and T-LGL leukemia (n = 42). Monoclonal TCRG/TCRB rearrangements in blood were identified in 11.3%/4.8% (7/3 of 62) of healthy individuals; 21.4%/14.3% (3/2 of 14) of patients with rheumatic diseases, and 17.6%/11.8% (3/2 of 17) of patients with reactive lymphocytosis. Immunomagnetic selection of lymphocytes in healthy individuals (31 of 33) revealed that clonal T-cells belong to CD8+ and CD57+ population. No clonal Vβ-Jβ TCRB rearrangements were found in the control group, only Dβ-Jβ TCRB and TCRG. Given the high detectability (96.7%) of Vβ-Jβ TCRB monoclonal rearrangements in patients with αβ-T-LGL leukemia, this marker had the greatest specificity and positive predictive value (100%; 99.2%). The presence of clonal CD8+CD57+ cells in blood is common for healthy individuals and patients with reactive conditions and may not associate with any malignancy. Different specificity of TCRG/ Dβ-Jβ TRB/ Vβ-Jβ TCRB PCR reactions should be taken into account for T-cell clonality data interpretation.

Keywords: PCR; T-cell large granular lymphocytic leukemia; TCR genes rearrangements; TCRB; TCRG.