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Blood, Vol. 94 No. 7 (October 1), 1999: pp. 2200-2207

BCR/ABL mRNA and the P210BCR/ABL Protein Are Downmodulated by Interferon-&b.alpha; in Chronic Myeloid Leukemia Patients

Fabrizio Pane, Ilaria Mostarda, Carmine Selleri, Rossella Salzano, Anna Maria Raiola, Luigia Luciano, Giuseppe Saglio, Bruno Rotoli, and Francesco Salvatore

From the CEINGE-Biotecnologie Avanzate, Dipartimento di Biochimica e Biotecnologie Mediche and Divisione di Ematologia, Facoltá di Medicina, Universitá Federico II, Naples; Dipartimento di Scienze Biomediche e Oncologia Umana, Universitá di Torino, Italy.

The BCR/ABL hybrid gene plays a central role in the pathogenesis of the chronic phase of chronic myeloid leukemia (CML). We used a very sensitive quantitative reverse transcriptase-polymerase chain reaction to investigate the levels of hybrid BCR/ABL mRNA in bone marrow cells of 20 patients with Philadelphia positive (Ph+) CML treated with interferon-alpha (IFN-alpha ) as a single agent. Bone marrow samples were collected at diagnosis and at hematologic remission induced by IFN-alpha , or by hydroxyurea in case of resistance to IFN-alpha . The mean levels of BCR/ABL transcripts in bone marrow mononuclear cells of patients who showed a complete hematologic response to IFN-alpha were significantly reduced with respect to those at diagnosis (48 × 103 v 168 × 103; P < .001), whereas no difference was detected between the values at diagnosis and at hematologic remission in patients resistant to IFN-alpha . In cell culture experiments, IFN-alpha priming significantly reduced the levels of BCR/ABL hybrid transcripts in a dose-dependent manner in Ph+ bone marrow precursors obtained at diagnosis from patients who subsequently responded to IFN-alpha treatment (P < .005). No downmodulation was observed in bone marrow precursors from patients who subsequently proved to be IFN-resistant. These results indicate that downmodulation of BCR/ABL gene expression could be one of the mechanisms involved in the response of CML patients to IFN-alpha treatment.


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