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

Abstract

For the management of chronic myeloid leukemia (CML), prediction or early determination of the response to interferon-alpha (IFN-alpha) 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-alpha receptor (IFN-alphaR2c) genes were analyzed at diagnosis in 74 patients with chronic phase CML treated with an IFN-alpha monotherapy. By using blood samples, real-time quantitative polymerase chain reaction was performed to quantify BCR-ABL, IFN-alphaR2c, and G6PDH mRNA as external control. The results were compared with hematologic and cytogenetic responses to IFN-alpha. 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-alpha was observed. In contrast, the variation of IFN-alphaR2c/G6PDH ratio at diagnosis was significantly associated with the achievement of major cytogenetic response (MCR; 34% or lower Ph(+) metaphases). Median values of IFN-alphaR2c/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). (Blood. 2001;97:3568-3573)

• Authors: C Barthe, F X Mahon, M J Gharbi, C Fabères, C Bilhou-Nabéra, A Hochhaus, J Reiffers, G Marit
• Journal: Blood (Blood) Vol. 97 Issue 11 Pg. 3568-73 (Jun 01 2001) ISSN: 0006-4971 [Print] United States
• PMID: 11369652 (Publication Type: Journal Article)

Chemical References

• Interferon-alpha
• RNA, Messenger
• Receptors, Interferon
• Glucosephosphate Dehydrogenase
• Fusion Proteins, bcr-abl

Topics

• Adult
• Aged
• Cytogenetic Analysis
• Female
• Fusion Proteins, bcr-abl (genetics)
• Gene Expression
• Glucosephosphate Dehydrogenase (genetics)
• Humans
• Interferon-alpha (therapeutic use)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (blood, drug therapy)
• Male
• Middle Aged
• Polymerase Chain Reaction
• RNA, Messenger (analysis, blood)
• Receptors, Interferon (genetics)
• Sensitivity and Specificity
• Tumor Cells, Cultured