The suppressor of cytokine signaling-1 is constitutively expressed in chronic myeloid leukemia and correlates with poor cytogenetic response to interferon-alpha

Abstract

BACKGROUND AND OBJECTIVES: Interferon-alpha (IFN-alpha) has proven useful for treating chronic myeloid leukemia (CML). However, only 7% of patients achieve a complete cytogenetic response. Although efforts to understand the molecular basis of this resistance to IFN-alpha have been made, the mechanism is still unknown. Because suppressor of cytokine signaling (SOCS) proteins are negative regulators of cytokine-induced signaling, it has been hypothesized that aberrant SOCS expression could confer resistance against cytokine therapy. DESIGN AND METHODS: In order to analyze the role of SOCS-1 in the acquisition of IFN-alpha resistance in this setting, we examined SOCS-1 mRNA expression using reverse transcription polymerase chain reaction (RT-PCR) in 75 newly diagnosed chronic phase-CML patients who received IFN-alpha therapy. RESULTS: SOCS-1 was constitutively expressed in 49 (65%) of 75 CML patients at diagnosis. Constitutive SOCS-1 expression was more frequently observed among Hasford high-risk patients (p = 0.05) and was also independently associated with a shorter median progression-free survival time (p = 0.001) and poor cytogenetic response to IFN-alpha treatment (p 0.0001). INTERPRETATION AND CONCLUSIONS: Our data indicate that constitutive expression of SOCS-1 occurs at an early stage in CML pathogenesis and probably influences the clinical behavior of the disease.