Levels of the soluble, 55‐kilodalton isoform of tumor necrosis factor receptor in bone marrow are correlated with the clinical outcome of children with acute lymphoblastic leukemia in first recurrence

Abstract

BACKGROUNDIt has been shown that the soluble, 55‐kilodalton isoform of tumor necrosis factor receptor (sTNFRp55) enhances tumor survival by exhibiting competitive ligand binding. The objective of the current study was to determine the levels of sTNFRp55 and their impact on outcome in 106 children with acute lymphoblastic leukemia (ALL) in first recurrence.METHODSBetween January 1997 and December 2001, bone marrow (BM) samples were collected from 106 children with a first recurrence of ALL at diagnosis. These patients were enrolled in the Berlin–Frankfurt–Münster (BFM) ALL recurrence trial, ALL‐REZ BFM 90‐96. Levels of sTNFRp55 in BM samples were determined with a commercially available enzyme‐linked immunosorbent assay kit. Event‐free survival (EFS) and overall survival were assessed from the date of study entry or the date of randomization, as appropriate.RESULTSThe mean sTNFRp55 level (± standard deviation) was 3.40 ± 2.57 ng/mL. High levels of sTNFRp55 were associated with shorter duration of first complete remission and observation time as well as poor response to chemotherapy. Most importantly, the probability of EFS (pEFS) at 3 years was significantly worse for children with recurrent ALL who had sTNFRp55 levels greater than the median value (> 2.77 ng/mL) compared with patients who had levels that were less than the median value (pEFS: 0.44 ± 0.10 ng/mL vs. 0.12 ± 0.10 ng/mL; P = 0.006). It is noteworthy that the sTNFRp55 levels in 22 children with recurrent, TEL‐AML1‐positive ALL ([t(12;21)(p13;q22)]; 2.69 ± 1.05 ng/mL) were significantly lower compared with the levels in children who had TEL‐AML1‐negative ALL (3.34 ± 1.49 ng/mL; P < 0.05).CONCLUSIONSThe results indicated that a high sTNFRp55 level represents a negative prognostic factor for children with recurrent ALL in terms of EFS and overall survival. Cancer 2003;98:625–31. © 2003 American Cancer Society.DOI 10.1002/cncr.11553

Protein Kinase Cε Inhibits UVR-Induced Expression of FADD, an Adaptor Protein, Linked to both Fas- and TNFR1-Mediated Apoptosis

“…Although TNF can signal through two receptors, TNFR1 and TNFR2, the majority of TNF-mediated biological events are mediated via TNFR1 signaling (Chen and Goeddel, 2002; Locksley et al ., 2001; MacEwan, 2002; Tartaglia and Goeddel, 1992; Vandenabeele et al ., 1995). Furthermore, TNFR1 plays an important role in the induction of several cancers (Arnott et al ., 2004; Figueras et al , 2005; Houtenbos et al , 2004; Lind et al ., 2004; Wu et al , 2003). TNFα and TNFR1 have been linked to UVR carcinogenesis (Moore et al , 1999; Suganuma et al , 1999; Starcher, 2000; Wheeler et al , 2004; Wheeler et al , 2005; Zhuang et al , 1999).…”

P38 MAPK/AKT signalling is involved in IL-33-mediated anti-apoptosis in childhood acute lymphoblastic leukaemia blast cells

“…Although treatment has improved drastically over the past few decades, approximately 20–25% of paediatric patients with ALL still experience disease relapse [ 17 , 18 ]. Recent studies have shown that aberrant expression of cytokines and their receptors in the tumour microenvironment contributes to clonal expansion of transformed lymphoid precursor cells, thus promoting the progression of leukaemia [ 5 , 19–21 ]. IL-33 has been shown to participate in different biological activities in both nonhematological and hematological malignancies [ 22–25 ].…”

“…In consonance with observations in other disease patterns, inflammatory microenvironment might prospectively promulgate leukaemia immune escape. Recent studies have demonstrated that abnormal expression of cytokines and/or activation of their receptors contribute to the onset and progression in several haematopoietic malignancies [ 5 , 6 ]. The expression of commonly studied cytokines such as vascular endothelial growth factor (VEGF), IL-6, and IL-10, were found to correlate with the outcomes of patients with chronic lymphocytic leukaemia (CLL), thus indicating the benefit of using cytokines as biomarkers for treatment efficacy monitoring [ 7 ].…”

svapls: an R package to correct for hidden factors of variability in gene expression studies

“…CD74 plays an important role in multiple myeloma and its higher expression induces tumor cell malignancy [13]. An isoform of the tumor necrosis factor TNFRSF1A is associated with the development of Acute Lymphoblastic Leukemia (ALL) in children [14]. Specifically, LCN2 has been found to be connected with Acute Myelogenous Leukemia (AML) [15].…”