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Blood, 1 June 2001, Vol. 97, No. 11, pp. 3568-3573
NEOPLASIA
Expression of interferon- (IFN-) receptor 2c at diagnosis
is associated with cytogenetic response in IFN--treated chronic
myeloid leukemia
Christophe Barthe,
François-Xavier Mahon,
Marie-José Gharbi,
Carole Fabères,
Chrystèle Bilhou-Nabéra,
Andreas Hochhaus,
Josy Reiffers, and
Gérald Marit
From the Laboratoire Universitaire d'Hématologie
and Laboratoire Greffe de Moelle, Université Victor Segalen
Bordeaux; Service des Maladies du Sang, Centre Hospitalier
Universitaire de Bordeaux; Hôpital Haut-Levêque, Pessac,
France; and III Medizinische Klinik, Fakultät für Klinische
Medizin Mannheim der Universität Heidelberg, Mannheim, Germany.
For the management of chronic myeloid leukemia (CML), prediction or
early determination of the response to interferon-alpha (IFN- )
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-
receptor (IFN-R2c) genes were analyzed at diagnosis in
74 patients with chronic phase CML treated with an IFN- monotherapy.
By using blood samples, real-time quantitative polymerase chain
reaction was performed to quantify BCR-ABL, IFN-R2c, and G6PDH mRNA
as external control. The results were compared with hematologic and cytogenetic responses to IFN-. 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- was observed. In contrast, the variation of IFN-R2c/G6PDH
ratio at diagnosis was significantly associated with the achievement of
major cytogenetic response (MCR; 34% or lower Ph+
metaphases). Median values of IFN-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 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).
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[Abstract]
[Full Text]
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