Spontaneous production of interleukin 1 activity by chronic lymphocytic leukemic cells

Uggla, C; Aguilar‐Santelises, Miguel; Rosén, Anders; Mellstedt, Håkan; Jondal, Mikael

doi:10.1182/blood.v70.6.1851.1851

Cited by 39 publications

(4 citation statements)

References 21 publications

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“…5, lanes 2 and 3). It had been suggested that Ibl~ expression by CLL cells was related to their leukemic transformation (18)(19)(20). Our PCR data with normal B cells refute that hypothesis and indicate that IL-1B expression occurs as a natural event in B cells (Fig.…”

Section: Discussionsupporting

confidence: 79%

“…A number of studies have suggested that growth factors and/or their receptors have a role in CLL. High concentrations of soluble IL2 receptors, for example, have been detected in the serum of CLL patients, and IL-1 production by CLL cells has been documented (17)(18)(19)(20)(21)(22)(23). Other studies have suggested a role for TNF in supporting the proliferation of CLL cells (24,25).…”

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confidence: 99%

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Genes for interleukin 7 are transcribed in leukemic cell subsets of individuals with chronic lymphocytic leukemia.

Frishman

Long

Knospe

et al. 1993

The Journal of Experimental Medicine

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SummaryRegulation of expression of interleukin 7 (IL-7) mRNA is aberrant in the leukemic subset of cells of chronic lymphocytic leukemia (CLL) patients. The entire coding sequence for IL-7 as well as an alternatively spliced IL-7 mRNA are transcribed in these leukemic cells. No IL-7 mRNA expression is detected in fresh peripheral blood mononuclear cells from normal individuals. Furthermore, the "normal" nonleukemic subsets of cells isolated from the same CLL patients also do not express IL-7 mRNA. The only subset of cells in which IL-7 mRNA is detected is the one that contains the leukemic cells themselves. The polymerase chain reaction was used to examine cytokine expression, and flow cytometry was used to purify the various subsets of peripheral blood mononuclear cells examined in these studies, as well as to examine IL-7 receptor expression. A proportion of the cells from the CLL patients express receptors that are capable of binding IL-7, whereas T cell-depleted normal cell preparations do not express receptors for IL-7 that are detectable with IL-7 fluorokines. The IL-7 receptor-bearing cells in CLL patients include a portion of leukemic cells and a fraction of the T cells, as well as some non-T, non-B cells. These findings suggest that IL-7 and IL-7 receptor expression in CLL may be relevant not only to growth regulation of the leukemic cells but to the immunological abnormalities that occur in the disease as well, possibly via the induction of inappropriate immune activity of IL-7 receptor-bearing cells.

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Section: Discussionsupporting

confidence: 79%

mentioning

confidence: 99%

Genes for interleukin 7 are transcribed in leukemic cell subsets of individuals with chronic lymphocytic leukemia.

Frishman

Long

Knospe

et al. 1993

The Journal of Experimental Medicine

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“…This antigen is normally expressed on the monocyte‐macrophage surface (Goyert et al , 1988) and works as a receptor for lipopolysaccharide (LPS) and LPS binding proteins (Wright et al , 1990) which stimulate these cells to synthesize and secrete immunoregulatory and inflammatory molecules such as IL‐1, IL6 and TNFα (Morrison & Ryan, 1987). We know that B‐CLL cells can secrete all these pro‐inflammatory cytokines (Morabito et al , 1987; Uggle et al , 1987; Callea et al , 1996; Foa et al , 1990). Furthermore, we found that the soluble form of CD14 (sCD14), which enhances the monocyte‐macrophage activity (Frey et al , 1992), is over‐expressed in B‐CLL sera (Callea et al , 1996).…”

Section: Discussionmentioning

confidence: 99%

Surface CD14 positivity in B‐cell chronic lymphocytic leukaemia is related to clinical outcome

et al. 1999

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Summary. The aberrant expression of the myelomonocytic antigen CD14 was investigated in 128 untreated patients diagnosed with B-cell chronic lymphocytic leukaemia (B-CLL). A cut-off value of 5´10 9 /l CD14-positive cells was chosen for statistical analysis because it showed the best discriminating power among patients with different clinical features. 56 cases had a CD14 cell count >5´10 9 /l. A signi®cant correlation was found between Rai and Binet stages and total tumour mass (TTM) score on one hand, and the absolute CD14 cell cut-off, on the other. This relationship was more evident in Rai 0±II and Binet A±B stages, where a CD14 cell count >5´10 9 /l was preferentially distributed among patients with a higher tumoral mass. In univariate analysis the survival probability at 5 and 10 years showed a signi®cant correlation with Rai and Binet stages, TTM score, CD14 absolute cell count and median age. The median overall survival (OS) was 63 months for patients with a CD14 cell count >5´10 9 /l and 136 months for those with a CD14 cell count < 5´10 9 /l. In the multivariate Cox regression model, Rai stage, age and CD14 cell count were independent signi®cant factors for the prediction of OS. Finally, when the same analysis was restricted to Rai stages 0±II, CD14 cell count was the only signi®cant independent parameter in¯uencing OS, with a relative death risk of 3´8. In conclusion, these data reveal that CD14represents an important marker for predicting OS in B-CLL patients and, therefore, we suggest that it should be included in the immunological characterization of B-CLL.

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“…B-CLL cells are cytokine producers in vitro as well as in vivo (Aguilar-Santelises et al, 1992Schena et al, 1992a, b;Uggla et al, 1987). Previously IL-1 IL-1, IL-6, IL-7, IL-8, IL-10, TNF and TGF have been shown to be produced by B-CLL cells under various conditions (Aguilar-Santelises et al, 1993;di Celle et al, 1994;Finke et al, 1993;Plate et al, 1993;Schena et al, 1992b).…”

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confidence: 99%

Interleukin‐10 mRNA expression in B‐cell chronic lymphocytic leukaemia inversely correlates with progression of disease

Sjøberg¹,

Aguilar‐Santelises

Sjögren³

et al. 1996

Br J Haematol

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Interleukin-10 (IL-10) has been shown in vitro to inhibit survival and spontaneous DNA synthesis in B-cell chronic lymphocytic leukaemia (B-CELL) cells by induction of programmed cell death. We have analysed the presence of mRNA transcripts for IL-10 in purified B-CLL cells from 35 patients by RT-PCR. Transcripts for IL-10 were detected in 11/20 patients with non-progressive disease. In cell preparations from patients with progressive B-CLL IL-10 mRNA were detected in only 2/15 samples (P < or = 0.01). The Epstein-Barr virus status of the cells did not account for the difference in IL-10 mRNA expression observed between the two groups of patients. Thus, IL-10 mRNA expression in leukaemic cells from patients with B-CLL was strongly associated with non-progressive disease. This finding may support other observations suggesting that IL-10 might be a candidate for immune therapy of progressive B-CLL.

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Spontaneous production of interleukin 1 activity by chronic lymphocytic leukemic cells

Cited by 39 publications

References 21 publications

Genes for interleukin 7 are transcribed in leukemic cell subsets of individuals with chronic lymphocytic leukemia.

Genes for interleukin 7 are transcribed in leukemic cell subsets of individuals with chronic lymphocytic leukemia.

Surface CD14 positivity in B‐cell chronic lymphocytic leukaemia is related to clinical outcome

Interleukin‐10 mRNA expression in B‐cell chronic lymphocytic leukaemia inversely correlates with progression of disease

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