Heterogeneity of large granular lymphocyte proliferations: morphological, immunological and molecular analysis in seven patients

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Abstract
The clinical, morphological, immunological and molecular features of seven patients with a stable picture of chronic granular lymphocytosis, observed over a period of up to 4 years, were studied. Mild splenomegaly was detected in one patient, while lymphoadenopathy and hepatomegaly were absent. Surface marker analysis showed in five patients the common membrane phenotype of granular T-cell lymphocytosis (T3 +, T4-, T8 +, Leu-7 +); of the remaining two, one presented an unusual phenotype (T3 +, T4 +, T8 +) and the other showed a marked positivity with the Leu-11 and M1 monoclonal antibodies, but lacked the T3, T4, T8 antigens. Three cases had a low (<30%) expression of the T1 antigen. Functional studies showed that the proliferative response to PHA and the NK function were reduced in four of the seven cases. Molecular analysis, performed in six cases, revealed a monoclonal rearrangement of the T-cell receptor β-chain gene in three, a polyclonal T-cell configuration in two and a germ-line arrangement in the last. All three monoclonal cases showed a depressed NK activity and two a reduced PHA response. The results of this study document the heterogeneity of granular lymphocyte expansions and suggest that the clonal or reactive nature of these often indolent proliferations, suspected on the basis of immunologic functional studies, may be recognized at the DNA level.