T-Cell Large Granular Lymphocyte Leukemias Have Multiple Phenotypic Abnormalities Involving Pan-T-Cell Antigens and Receptors for MHC Molecules

Abstract

T-cell large granular lymphocyte (T-LGL) leukemias represent monoclonal T-cell expansions that express CD16, CD56, or CD57 and cause cytopenias. The identification of T-LGL leukemias can be difficult because reactive T-LGL cells also can express CD16, CD56, and CD57, and many leukemia cases show only mild lymphocytoses. In this study, 23 T-LGL leukemia cases were analyzed by 3- and 4-color flow cytometry to identify markers that could aid in discriminating leukemic from normal T-LGL. In most cases (18/23), abnormalities (bright, dim, or negative expression) of 2 or more pan-T-cell antigens were identified, with all cases showing abnormal CD5 levels. Abnormal expression of CD94 was identified in 22 of 23 cases, and 15 of 21 cases also showed abnormal expression of class 1 MHC receptor molecules identified by antibodies against CD158a, CD158b, CD158e, CD158i, CD158k, and CD94. These studies help define abnormal phenotypic features typical of T-LGL leukemia that may have important diagnostic value.

The pathogenesis and treatment of large granular lymphocyte leukemia

“…These markers support a constitutively active T cell phenotype 50, 51 . CD45 and CD62L markers can be used to distinguish naïve T cells, central memory, effector memory, and effector T cell populations 52 .…”

A unique CD4+ large granular lymphocytosis occurring in patients treated with tumor necrosis factor α inhibitors: report of 2 cases

“…Normal reactive T-LGLs are CD8 + T cells that coexpress the T-cell markers CD2, CD3, CD5, CD7, and TCRαβ, without CD4, CD16, or CD56. In contrast, classic T-LGL leukemia is composed of atypical CD8 + T cells frequently with altered expression levels of 2 or more T-cell markers and aberrant coexpression of CD16 and CD57 without CD4 or CD56 [7]. Most patients with classic CD8 + T-LGL leukemia present with cytopenias, usually neutropenia, and a mild peripheral blood lymphocytosis.…”

Mature T-cell leukemias: Molecular and Clinical Aspects

“…The neoplastic cells often exhibit expression of CD8, cytotoxic markers (granzyme, TIA-1, perforin), CD57, and CD16. Most cases are composed of αβ T-cells; however, rare γδ T-LGLL cases exist [31]. As the T-LGLL immunophenotype overlaps somewhat with that of nonclonal LGLs, establishing a diagnosis of T-LGLL may be challenging.…”

“…I n c o n t r a s t , c l i n i c a l l y s i m i l a r c h r o n i c lymphoproliferative disorders of NK cells (CLPD-NK) have T-cell receptor genes in a germline, non-rearranged configuration [32]. Both T-LGLs and NK cells express killer immunoglobulin-like receptors (KIRs) and assessment of KIR receptor expression by flow cytometry may have diagnostic utility in both T-LGLL and CLPD-NK [31,33]. In some cases, the diagnosis may be considered in the appropriate clinical situation, even if all disease criteria are not met [30].…”