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

For the management of chronic myeloid leukemia (CML), prediction or early d etermination of the response to interferon-alpha (IFN-alpha) treatment is i mportant for identifying nonresponder patients to whom alternative therapy may be proposed. In this study, the levels of expression of both BCR-ABL an d subunit 2c of IFN-alpha receptor (IFN-alpha R2c) genes were analyzed at d iagnosis in 74 patients with chronic phase CML treated with an IFN-alpha mo notherapy. By using blood samples, real-time quantitative polymerase chain reaction was performed to quantify BCR- ABL, IFN-alpha R2c, and G6PDH mRNA as external control. The results were compared with hematologic and cytogen etic responses to IFN-alpha, A wide variation in the BCR-ABL/G6PDH ratio wa s observed at diagnosis (median, 6.68%; range, 0.18%-41.31 %), but no signi ficant association with response to IFN-alpha was observed, In contrast, th e variation of IFN-alpha R2c/G6PDH ratio at diagnosis was significantly ass ociated with the achievement of major cytogenetic response (MCR; 34% or low er Ph+ metaphases). Median Values of IFN-alpha R2c/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 co mplete hematologic response at 3 months, makes it possible to predict MCR a chievement with high probability by Kaplan-Meier analysis (91% +/- 17% at 2 4 months; P = .0001), (Blood.2001;97:3568-3573) (C) 2001 by The American So ciety of Hematology.