TY - JOUR
T1 - Molecular follow-up of disease progression and interferon therapy in chronic myelocytic leukemia
AU - Ben-Yehuda, Dina
AU - Krichevsky, Svetlana
AU - Rachmilewitz, Eliezer A.
AU - Avraham, Ayelet
AU - Palumbo, Giuseppe A.
AU - Frassoni, Francesco
AU - Sahar, Dvora
AU - Rosenbaum, Hanna
AU - Paltiel, Ora
AU - Zion, Michal
AU - Ben-Neriah, Yinon
PY - 1997/12/15
Y1 - 1997/12/15
N2 - 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 α (IFNα) 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 IFNα-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 IFNα 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 IFNα therapy far better than the cytogenetic response.
AB - 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 α (IFNα) 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 IFNα-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 IFNα 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 IFNα therapy far better than the cytogenetic response.
UR - http://www.scopus.com/inward/record.url?scp=0031454221&partnerID=8YFLogxK
U2 - 10.1182/blood.v90.12.4918.4918_4918_4923
DO - 10.1182/blood.v90.12.4918.4918_4918_4923
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C2 - 9389709
AN - SCOPUS:0031454221
SN - 0006-4971
VL - 90
SP - 4918
EP - 4923
JO - Blood
JF - Blood
IS - 12
ER -