American Journal of Hematology 33:18-26 (1990) Procollagen Type zyxw 111 Aminoterminal Peptide in Serum in Idiopathic Myelofibrosis and Allied Conditions: Relation to Disease Activity and Effect of Chemotherapy H. Hasselbalch, P. Junker, K. Herslev-Petersen, I. Lisse, and K.D. Bentsen Departments of Medicine and Haematology C, Gentofte University Hospital (H.H.), Department of Medicine, Svendborg Hospital (P.J.), and Departments of Rheumatology (K.H.-P., K.D.B.) and Pathology (I.L.), Hvidovre University Hospital, Copenhagen The serum concentration of the aminoterminal propeptide of type 111 procollagen (PIIINP) was measured serially in patients with idiopathic myelofibrosis and other myeloprolifer- ative syndromes. Two different assays were applied, the RIA-gnost assay (Hoechst, Frankfurt, FRG) and a new equilibrium RIA for the N-terminal propeptide of human type 111 procollagen (Farmos Diagnostica, Oulu, Finland). A positive correlation was found between the results obtained by the two RIA’S (rho=0.90, P < 0.001). The highest propeptide levels were recorded in patients with idiopathic myelofibrosis, particularly in those with active disease. Elevated serum PlllNP levels decreased during treatment with various cytotoxic drugs, including intensive che- motherapy. By contrast, serum PlllNP was unchanged or increased in patients undergo- ing interferon alpha-2b therapy. Gel filtration of sera on Sephacryl zyxwvu S-300 column (Pharmacia, Sweden) showed that smaller PlllNP related peptides dominated in healthy subjects and in osteomyelosclero- sis with stable disease. Conversely, the relative proportion of intact propeptide increased in accelerating disease stages and acute myelofibrosis. In conclusion, the present study implicates serum PlllNP as a useful indicator of dis- ease activity in idiopathic myelofibrosis. The propeptide also appears to be a sensitive sero-marker of chemotherapy effect on fibrogenesis related to clonal myeloproliferation. Finally, the propeptide is suggested as an early predictor of relapse during cytotoxic therapy. Key words: procollagen 111 peptide, disease activity, myelofibrosis INTRODUCTION zyxwvutsrq In recent years the aminoterminal propeptide of type zyxwvu 111 procollagen (PIIINP) has been suggested as a sero- marker of the fibroproliferative activity in the bone mar- row in various myelofibrosing disorders [ 1-61, In cross- sectional studies, a significant correlation between the serum concentration of the propeptide and the leucocyte count has been found, indicating a relationship between fibrogenesis and the activity of the clonal myeloprolifer- ation (1,4,5]. This relationship as well as the influence of chemotherapy on serum PIIINP (S-PIIINP) remain to be studied prospectively in a larger series of patients. The radioimmunoassay (RIA-gnost, Hoechst, FRG) used in most previous studies on circulating PIIINP 171 does not exclusively detect the authentic propeptide re- lcascd during conversion of procollagen to collagen. Thus. the assay system has the disadvantage of measur- ing at least three molecular weight variants of the anti- gen, including both higher and lower molecular weight peptides. The latter may represent degradation products of the propeptide [8]. Recently, a new equilibrium RIA (Farmos Diagnostica, Oulu, Finland) based on human PIIINP has been introduced by Risteli et al. “,I. This assay system does not detect the small degradation prod- ucts of the aminoterminal propeptide, but only serum antigens of a size similar to the intact propeptide or larger [9]. The relative contribution of these antigens to the Received for publication April 19, 19x9; accepted August 17, 1989. Address reprint requests to Dr. Hans Hasselbalch, Department of Medicine B. Bispebjerg Hospital, 2400, Copenhagen, Denmark. zy 0 1990 Alan R. Liss, Inc.