PHILADELPHIA-CHROMOSOME-POSITIVE CHRONIC MYELOGENOUS LEUKEMIA - FUNCTIONAL DEFECTS IN CIRCULATING MATURE NEUTROPHILS OF UNTREATED AND INTERFERON-ALPHA-TREATED PATIENTS

This study focuses on possible functional defects of circulating matur e neutrophils in chronic phase chronic myelogenous leukemia (CML) and their modulation by interferon-alpha (IFN-alpha). Polymorphonuclear ce lls (PMN) of seven untreated and nine IFN-alpha-treated patients were evaluated for the following parameters by the following methods: gener ation of oxygen species, by luminol-dependent chemiluminescence; leuko triene B-4 (LTB(4)) generation, by high-performance liquid chromatogra phy (HPLC); expression of LTB(4) and formylmethionyl-leucyl phenylalan ine (FMLP) receptor sites, by H-3-binding assay; and GTPase activity, by P-32-gamma-GTP. Compared to normal controls, reduced values were ob tained in treated and untreated CML for most parameters studied. Thera py with IFN-alpha resulted in significantly diminished values for oxyg en species (NaF stimulation) and LTB(4) (FMLP stimulation) generation, as well as FMLP receptor expression as compared to untreated CML. We conclude that alterations at the level of oxygen species production, m ediator generation, receptor expression, and transmembrane signaling a re involved in functional defects of circulating mature neutrophils fr om CML patients. IFN-alpha seems to enhance some of these functional d efects, but the clinical relevance of these findings has to be elucida ted.