Haematopoietic progenitors and signal transduction in polycythaemia vera and primary thrombocythaemia

While significant progress has been made in understanding the cellular defe ct and molecular basis of polycythaemia vera (PV), elucidation of the prima ry mutation leading to PV remains elusive. While clinically useful, the PV diagnostic criteria put forward by the Polycythemia Vera Study Group are no t based on the pathophysiology of this disorder and in some instances may l ead to false diagnosis or may not be sufficient to diagnose an early PV. In diagnostically unclear situations, clinical and laboratory findings must t ake into account the acquired nature of PV, its clonality, and the presence of endogenous erythroid colony formation in serum-containing media. It is likely that other simpler assays may be developed based on the rapidly emer ging knowledge of the cellular pathology of PV. Several intriguing observat ions of abnormalities pertaining to the erythroid signal transduction have been recently reported; these remain to be validated in other laboratories and to be proven specific for PV. The clinical concept of primary thrombocy thaemia (PT) lags behind what we know about PV. While the diagnosis of PT i s still based on the exclusion of other known causes of thrombocytosis, new knowledge is emerging. Recent clonality studies of a large number of PT fe males show that the majority are clonal. It is our belief that thrombocytha emic subjects who are not found to be clonal are those with secondary throm bocytosis. Multiple in vitro-based assays of megakaryocytic and erythroid p rogenitors have been developed and conflicting data published. It is likely that standardized assays of megakaryocytic progenitors will soon become av ailable and a reproducible PT specific defect will be found. Such a specifi c test would be of immense diagnostic value in this most elusive of all mye loproliferative disorders.