EXPRESSION OF C-FOS CORRELATES WITH IFN-ALPHA RESPONSIVENESS IN PHILADELPHIA-CHROMOSOME-POSITIVE CHRONIC MYELOGENOUS LEUKEMIA

This study evaluates (i) constitutive levels of oncogene and p53 trans cripts in chronic phase CML patients and (ii) their modulations subseq uent to in vivo therapy with rIFN-alpha 2c. Peripheral blood mononucle ar cells (pbmc) and bone marrow cells of 26 patients were examined for c-fos, c-myc, p53 and the hybrid bcr/abl mRNA levels. Results indicat ed that (i) constitutive c-fos transcript levels are significantly hig her in patients subsequently responding to IFN-alpha therapy (p < 0.01 ) and are positively correlated with the proportion of lymphocytes (r = 0.6895, p < 0.01) and negatively with the proportion of immature cel ls (r = -0.568, p < 0.01) contained in the pbmc preparations tested, ( ii) constitutive mRNA levels of the hybrid bcr/abl, c-myc and p53 are positively correlated with each other, but failed to relate to disease parameters, and (iii) acute and chronic in vivo exposure to IFN-alpha is accompanied by upregulation of c-fos and downregulation of c-myc m RNA levels in responder patients.