INCREASED EXPRESSION OF THE DIFFERENTIATION-DEFECTIVE GRANULOCYTE-COLONY-STIMULATING FACTOR-RECEPTOR MESSENGER-RNA ISOFORM IN ACUTE MYELOGENOUS LEUKEMIA

Granulocyte colony-stimulating factor (G-CSF) critically affects all s tages of granulopoiesis by activating a signaling cascade initiated by dimerization of its receptor (G-CSFR). Five human G-CSFR isoforms hav e been identified (classes I-V). A quantitative polymerase chain react ion (Q-PCR) technique was used to examine the expression of these five isoforms in normal and leukemic myeloid cells. We demonstrated that n eutrophils expressed predominantly the class I isoform and low levels of class IV isoform (IV/I=0.037 +/- 0.005). No expression of the class II, class III, or class V isoform was detected. In contrast, all AML cell lines and acute myelogenous leukemia (AML) patient samples expres sed increased relative amounts of the class IV isoform (IV/I=0.047-0.3 50). When compared to normal immature myeloid cells, as represented by the CD34(+) fraction of adult bone marrow (ABM) cells, three of eight AML cell lines and three of six AML patient samples expressed signifi cantly increased levels of the class IV isoform relative to class I. T his suggests that the increase in the relative expression of the class IV isoform seen in a considerable portion of AML cell samples is rela ted to their leukemic phenotype. Given the inability of the class IV G -CSFR to drive myeloid maturation, the relative increase in class IV e xpression in AML cells may contribute to their aberrant response to G- CSF.