DIFFERENTIAL EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA, BASIC FIBROBLAST GROWTH-FACTOR, AND THEIR RECEPTORS IN CD34(+) HEMATOPOIETIC PROGENITOR CELLS FROM PATIENTS WITH MYELOFIBROSIS AND MYELOID METAPLASIA

Myelofibrosis with myeloid metaplasia (MMM) is a myeloproliferative di sorder characterized by clonal expansion of hematopoiesis and marrow f ibrosis. Previous results from our group have shown an increased produ ction of two potent fibrogenic factors also involved in the regulation of primitive hematopoietic cells, namely transforming growth factor-p i (TOP-pi) and basic fibroblast growth factor (bFGF), in patients with MMM. It is likely to assume that the myeloproliferation characteristi c of this disease may result from an abnormal proliferation of CD34(+) hematopoietic progenitors. Thus, we were particularly concerned in st udying the gene and protein expression of these cytokines and their re ceptors in CD34(+) progenitors purified from the peripheral blood of M MM patients by using semiquantitative reverse transcriptase-polymerase chain reaction and immunolabeling methods. Our data showed that the e xpression of TGF-beta 1 is not altered in patients CD34(+) cells; in c ontrast, the expression of TGF-beta type II receptor is significantly decreased in such cells, as compared with CD34(+) cells from healthy s ubjects, Regarding bFGF, the very low expression of the cytokine and i ts type I and II receptors detected in normal CD34(+) cells contrasts with that observed in patients' CD34(+) cells, which is significantly higher, Our results might be a clue for a better understanding of the mechanism(s) involved in the dysregulation of hematopoiesis in MMM. Ac tually, the increased expression of bFGF and its receptors associated with the reduction of the TGF-beta binding receptor in CD34(+) progeni tors from MMM patients might facilitate the expansion of hematopoietic progenitors, not only by stimulating their growth and/or survival, bu t also by overcoming negative regulatory signals. (C) 1996 by The Amer ican Society of Hematology.