Expression of c-fos correlates with IFN-alpha responsiveness in Philadelphia chromosome positive chronic myelogenous leukemia

Cytokines Mol Ther. 1995 Mar;1(1):29-38.

Abstract

This study evaluates (i) constitutive levels of oncogene and p53 transcripts in chronic phase CML patients and (ii) their modulations subsequent to in vivo therapy with rIFN-alpha 2c. Peripheral blood mononuclear 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 indicated that (i) constitutive c-fos transcript levels are significantly higher in patients subsequently responding to IFN-alpha therapy (p < 0.01) and positively correlated with the proportion of lymphocytes (r = 0.6895, p < 0.01) and negatively with the proportion of immature cells (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 mRNA levels in responder patients.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Fusion Proteins, bcr-abl / biosynthesis
  • Humans
  • Interferon Type I / adverse effects
  • Interferon Type I / therapeutic use*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Leukocyte Count
  • Leukocytes, Mononuclear / metabolism
  • Oncogenes
  • Platelet Count
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • RNA, Messenger / biosynthesis
  • Recombinant Proteins
  • Risk Factors
  • Transcription, Genetic*
  • Tumor Suppressor Protein p53 / biosynthesis

Substances

  • Interferon Type I
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Recombinant Proteins
  • Tumor Suppressor Protein p53
  • Fusion Proteins, bcr-abl