Interleukin-10 Gene Expression Predicts Response to Therapy in Childhood Acute Lymphoblastic Leukemia

Abstract

Several studies have demonstrated that IL-10 have been associated with therapy outcome in hematological malignancies. IL-10 might therefore also correlate with clinical outcome in childhood acute lymphoblastic leukemia (ALL). In addition to expressing full-length IL-10, a new splicing-derived IL-10 variant  (termed IL-10δ3) can be detected in ALL samples. These isoforms generally have different affinities to their receptors, contributing to generating important  function in modulating the biologic activity of normal IL-10.

 Most childhood malignancies lack reliable and specific biochemical tumor markers correlating with disease extent and aggressiveness. That is why several non-specific indirect indicators, including ESR, CRP and LDH, are used in common practice as additional diagnostic and prognostic tools. The study presented here aimed to assess whether the expression of IL-10 and its isoform, IL-10δ3 correlate with other prognostic factors. Mainly, the response to treatment and  risk of relapse in 60 children with B-cell precursor (BCP)-ALL, treated at the Pediatric Oncology Department, National Cancer Institute, Cairo University and Damnhour Teaching hospital (DMNI) during the time period from August 2009 to May 2014 according to NCI protocols modified from the St. Jude Total XV protocols. The median age of the patients was 6 years (range, 0.91 years to 24 years) and the male: female ratio was 1.61:1 (37 males and 23 females).

Study data showed a possible role of IL-10δ3 particularly decreased incidence of relapse and prolonged event-free survival in first complete remission, whereas no association between response to therapy and IL-10 and IL-10 isoform, IL-10δ3, expression. Moreover, CD34 expression with a good prognosis was higher in patients displaying IL-10δ3 expression compared to patients not expressing the isoform. 

Results revealed correlation between pro-B stage and IL-10δ3 expression (the 4 patients with pro-B stage expressed IL-10δ3). This relation was not clear since the pro-B immunophenotype is often associated with unfavorable outcome and IL-10δ3 was linked to better clinical outcomes and prolonged event free survival at relapse and first complete remission. May be IL-10δ3 expression reversed bad prognosis.

 In childhood B-cell precursor (BCP)-ALL, IL-10 isoform, IL-10δ3, expression was associated with a favorable prognosis, better event-free survival and decreased the incidence of relapse in first complete remission.