Constitutive expression of the interleukin-6 gene in chronic lymphocytic leukemia

Abstract

Interleukin-6 (IL-6) is a pleiotropic lymphokine active as a growth factor on B-cell hybridomas and plasmacytomas and found to be identical with B-cell stimulatory factor 2, interferon beta 2, 26-Kd protein, and hepatocytes stimulating factor. IL-6 gene expression was investigated in fresh human chronic lymphocytic leukemia (B-CLL) and in acute lymphoblastic leukemia (ALL) by Northern blot analysis using a specific cDNA probe. 1.3-kb IL-6 transcript was found in six out of 11 B-CLL patients, while no hybridization was observed in ten cases of ALL of both T- and B-cell origin. The constitutive expression of IL-6 transcripts was associated with production of a biologically active protein as determined by using the IL-6-dependent 7TD1 cell line. It remains to be elucidated whether IL-6 gene expression is indeed important in the regulation of B-CLL growth or in its clinical manifestation.

Interleukin 6 (IL‐6) and its receptor: Their role in plasma cell neoplasias

“…A possible autocrine role for IL-6 was also reported in non-Hodgkins lymphomas, chronic lymphocytic leukemias and acute myeloid leukemias [79, IL-6 was also demonstrated to be an autocrine growth factor for EBV-transformed B cell lines [89] and expression of an exogenous IL-6 gene in these B cell lines conferred growth advantage and in vivo tumorigenicity [90]. However, it has been controversial whether all myeloma cells actually produce IL-6, because only some myeloma cell lines were found to produce IL-6 [76,91-931, and bone marrow-adherent cells (rather than bone marrow nonadherent cell populations [86][87][88].…”

IL4 production and increased CD30 expression by a unique CD8+ T‐cell subset in B‐cell chronic lymphocytic leukaemia

“…Changes in the cytokine network between malignant cells and residual T lymphocytes could sustain the expansion of the leukaemic B-cell clone. Accordingly, there is evidence to suggest that cytokines may participate in auto/paracrine loops affecting CLL cell growth (Digel et al, 1989;Foa et al, 1990;Biondi et al, 1989;Aguilar-Santelises et al, 1991;Aderka et al, 1993;Francia di Celle et al, 1994). The expression of cytokine receptors, such as the high-affinity interleukin 2 (IL2) receptor (R) complex a, b, g (de Totero et al, 1995), on CLL cells but not on normal resting B cells, further supports this contention.…”

Increased spontaneous secretion of IL-6 from B cells of patients with B chronic lymphatic leukaemia (B-CLL) and autoimmunity

“…Recently, Freeman et al (1989) observed IL-6 gene expression in several B cell malignancies, but not in B-CLL. In contrast, Biondi et al (1989) found that B cells from a significant proportion of B-CLL patients constitutively express IL-6 gene and secrete variable amounts ofthe biologically active protein.…”