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Molecular Follow-Up of Disease Progression and Interferon Therapy in Chronic Myelocytic Leukemia
Dina Ben-Yehuda,
Svetlana Krichevsky,
Eliezer A. Rachmilewitz,
Ayelet Avraham,
Giuseppe A. Palumbo,
Francesco Frassoni,
Dvora Sahar,
Hanna Rosenbaum,
Ora Paltiel,
Michal Zion, and
Yinon Ben-Neriah
From the Departments of Hematology and Social Medicine, Hadassah Hospital and The Lautenberg Center for Immunology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel; Institute of Hematology, University of Catania, Ospedale San Martino, Genova, Italy; and the Department of Hematology, Rambam Medical Center, Haifa, Israel.
We previously reported that the abl promoter (Pa) undergoes de novo DNA methylation in the course of chronic myelocytic leukemia (CML). The clinical implications of this finding are the subject of the present study in which samples of CML patients, including a group treated with interferon  (IFN) were surveyed. The methylation status of the abl promoter was monitored by polymerase chain reaction (PCR) amplification of the Pa region after digestion with several site-methylation sensitive restriction enzymes. Some 74% of the DNA samples from blood and marrow drawn in the chronic phase were nonmethylated, similar to control samples from non-CML patients. The remaining 26% were partially methylated in the abl Pa region. The latter samples were derived from patients who were indistinguishable from the others on the basis of clinical presentation. Methylated samples were mostly derived from patients known to have a disease of longer duration (26 months v 7.5 months, P = .01). Samples of 30 IFN-treated patients were sequentially analyzed in the course of treatment. Fifteen patients with no evidence of Pa methylation before treatment remained methylation-free. The remainder, who displayed Pa methylation before treatment, reverted to the methylation-free status. The outcome is attributed to IFN therapy, as the Pa methylation status was not reversed in any of the patients treated with hydroxyurea. Methylation of the abl promoter indicates a disease of long-standing, most likely associated with a higher probability of imminent blastic transformation. It appears to predict the outcome of IFN therapy far better than the cytogenetic response.
Blood, Vol. 90 No. 12 (December 15), 1997:
pp. 4918-4923
© 1997 by The American Society of Hematology.
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