Detection of IL4 and TNFA and their receptors in chronic lymphocytic leukemia of B lineage

Abstract

Chronic lymphocytic leukemia of B cell lineage (B-CLL) is a common neoplasm of the elderly, in which rising lymphocytosis, in combination with a low proliferation rate, point to an abnormally long life span of the B-CLL lymphocytes. No etiologic cytogenetic abnormality has been detected thus far for B-CLL, suggesting that tumor environmental factors and intercellular signaling processes may be important in its pathogenesis. 'Purpose'. This study focuses in the role of tumor generated cytokines as modulators in the neoplastic cell biology. In particular, the potential of B-CLL lymphocytes to produce two cytokines previously implicated in cell survival and proliferation: IL4 and TNF_, as well as to express their surface receptors. 'Method'. Peripheral blood samples from 44 untreated B-CLL patients were analyzed to determine expression of intracellular IL4 and TNF_ and their receptors in the B-CLL lymphocytes, using a standard flow cytometric technique. Levels were correlated with the clinical stage of the disease. Results'. In most cases of indolent B-CLL, the tumor cell populations showed a large proportion of IL4 receptor and intracellular IL4 positive cells, while intracellular TNF_ and TNF_ receptor were detected only in a small subset of tumor cells. In contrast, the aggressive stage cases showed decreased levels of intracellular IL4, and a slightly lower proportion of IL4 receptor positive cells. Intracellular TNF_ and its receptor expression were increased in these high risk B-CLL populations. These findings parallel the traditional knowledge of population subsets in B-CLL: a majority of non-dividing, long lived cells, with a small proliferating pool in the low risk cases, changing to an increased proportion of proliferating cells in high risk B-CLL. This study suggests that B-CLL produced IL4 may support apoptosis resistance in the accumulating cells, while TNF_ generated by some of the B-CLL cells could foster the proliferating subset.