High expression of suppressor of cytokine signaling-2 predicts poor outcome in pediatric acute myeloid leukemia: a report from the Children's Oncology Group

Abstract

Deregulated cytokine signaling is a characteristic feature of acute myeloid leukemia (AML), and expression signatures of cytokines and chemokines have been identified as a significant prognostic factor in this disease. Given this aberrant signaling, we hypothesized that expression of suppressor of cytokine signaling-2 (SOCS2), a negative regulator of cytokine signaling, might be altered in AML and could provide predictive information. Among 188 participants of the Children's Oncology Group AAML03P1 trial, SOCS2 mRNA levels varied > 6000-fold. Higher (> median) SOCS2 expression was associated with inferior overall (60 ± 10% vs. 75 ± 9%, p = 0.026) and event-free (44 ± 10% vs. 59 ± 10%, p = 0.031) survival. However, these differences were accounted for by higher prevalence of high-risk and lower prevalence of low-risk disease among patients with higher SOCS2 expression, limiting the clinical utility of SOCS2 as a predictive marker. It remains untested whether high SOCS2 expression identifies a subset of leukemias with deregulated cytokine signaling that could be amenable to therapeutic intervention.

Keywords::

• SOCS2
• cytokine
• acute myeloid leukemia
• prognostic factor
• childhood cancer

Acknowledgements

We thank Sommer Castro and the COG AML Reference Laboratory for providing diagnostic AML specimens.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal

This study was supported by a grant from the National Cancer Institute/National Institutes of Health (P30-CA015704-35S6, U10-CA098543-08, and U24-CA114766).