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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- 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- (IFN- ) as a
single agent. Bone marrow samples were collected at diagnosis and at
hematologic remission induced by IFN- , or by hydroxyurea in case of
resistance to IFN- . The mean levels of BCR/ABL transcripts in bone
marrow mononuclear cells of patients who showed a complete hematologic response to IFN- 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- . In cell culture
experiments, IFN- 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- 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- treatment.

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