Expression of interferon-α (IFN-α) receptor 2c at diagnosis is associated with cytogenetic response in IFN-α–treated chronic myeloid leukemia

Abstract

For the management of chronic myeloid leukemia (CML), prediction or early determination of the response to interferon-alpha (IFN-α) treatment is important for identifying nonresponder patients to whom alternative therapy may be proposed. In this study, the levels of expression of both BCR-ABL and subunit 2c of IFN-α receptor (IFN-αR2c) genes were analyzed at diagnosis in 74 patients with chronic phase CML treated with an IFN-α monotherapy. By using blood samples, real-time quantitative polymerase chain reaction was performed to quantify BCR-ABL, IFN-αR2c, and G6PDH mRNA as external control. The results were compared with hematologic and cytogenetic responses to IFN-α. A wide variation in the BCR-ABL/G6PDH ratio was observed at diagnosis (median, 6.68%; range, 0.18%-41.31%), but no significant association with response to IFN-α was observed. In contrast, the variation of IFN-αR2c/G6PDH ratio at diagnosis was significantly associated with the achievement of major cytogenetic response (MCR; 34% or lower Ph+metaphases). Median values of IFN-αR2c/G6PDH ratio for patients achieving MCR and for those who did not achieve it were 110.75% (range, 9.47%-612.30%) and 64.42% (range, 5.96%-425.40%), respectively (P = .037). In addition, this novel molecular factor, combined with the achievement of complete hematologic response at 3 months, makes it possible to predict MCR achievement with high probability by Kaplan-Meier analysis (91% ± 17% at 24 months; P = .0001).