Sequential therapy with recombinant interferons gamma and alpha in patients with unfavorable prognosis of chronic myelocytic leukemia: clinical responsiveness to recombinant IFN-alpha correlates with the degree of receptor down-regulation.

Abstract

Natural and recombinant interferons (IFNs) have already demonstrated therapeutic efficacy, including cytogenetic remissions, in patients with chronic myelocytic leukemia (CML). We investigated at the level of ligand-receptor interaction the question whether heterogeneity of receptor number or affinity might contribute to primary or secondary treatment failures in CML. We therefore analyzed IFN-gamma and IFN-alpha receptor expression and regulation during treatment with recombinant IFN-gamma and IFN-alpha in 15 patients with advanced CML. We found no difference in number or affinity of constitutively expressed IFN-gamma receptors (mean 1,100) and, on average, a 30% reduction of IFN-alpha receptors (mean 750) on peripheral blood mononuclear cells (PBMNC) of patients with chronic or accelerated CML as compared to mature granulocytes and/or bone marrow cells of healthy controls, which express on average 1,050 and 1,100 IFN-gamma and IFN-alpha receptors, respectively. While IFN-gamma receptor expression on PBMNC is not influenced upon treatment with rIFN-gamma, there is a substantial downregulation of IFN-alpha receptors in the course of rIFN-alpha therapy. Our data also show a differential pattern of receptor downregulation between patients achieving complete hematologic remission (CHR) (4 out of 12) compared with patients with partial hematologic remission (PHR) and non-responders. We conclude that differences in IFN receptor number cannot explain primary or secondary treatment failures. However, the differential ligand induced downregulation of IFN-alpha receptors in patients achieving CHR compared to those with PHR or non-responders suggest a prospective value of IFN-alpha receptor determination.

• Authors: H H Bartsch, K Pfizenmaier, A Hanusch, P Scheurich, U Ucer, G A Nagel
• Journal: International journal of cancer (Int J Cancer) Vol. 43 Issue 2 Pg. 235-40 (Feb 15 1989) ISSN: 0020-7136 [Print] United States
• PMID: 2521842 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Interferon Type I
• Receptors, Immunologic
• Receptors, Interferon
• Interferon-gamma

Topics

• Adult
• Aged
• Clinical Trials as Topic
• Drug Administration Schedule
• Female
• Humans
• Interferon Type I (administration & dosage, adverse effects, therapeutic use)
• Interferon-gamma (administration & dosage, adverse effects, therapeutic use)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (blood, therapy)
• Male
• Middle Aged
• Prognosis
• Receptors, Immunologic (metabolism)
• Receptors, Interferon