Clonality markers in polycythaemia and primary thrombocythaemia

Our current understanding of the pathogenesis of the myeloproliferative disorders is based on the assumption that they represent a clonal disorder resulting from transformation of a haematopoietic stem cell. Clonality assays exploit the fact that female cells have only one active X-chromosome. Methods for determining X chromosome inactivation have been devised at the protein (G6PD isoenzymes); DNA (HUMARA; phosphoglycerate kinase (PGK); hypoxanthine-phosphoribosyl transferase (HPRT) and RNA (G6PD; P55; IDS) levels. In this type of RNA assay the product of the active X chromosome is quantified by studying polymorphisms present in mRNA. The presence of skewed lyonization in normal females is a potential limitation to the method, although the use of T cells as a control makes it possible to distinguish clonal haematopoiesis from skewed lyonization. However, the phenomenon of acquired skewing in normal elderly women means that X-inactivation patterns in elderly patients must be interpreted with caution. Clonality studies have been conducted in polycythaemia vera (PV) and essential thrombocythaemia (ET) patients. They usually demonstrate a clonal X-inactivation pattern in granulocytes and/or platelets but a polyclonal pattern in T cells. However, in both ET and PV a significant minority of patients exhibit polyclonal haematopoiesis with polyclonal patterns in granulocytes/platelets. Female patients with polyclonal haematopoiesis differ from those with clonal haematopoiesis in terms of age and platelet count and possibly in their requirements for treatment. This new technology for the investigation of the MPD seems promising for understanding certain clinical aspects of these diseases and may be introduced for evaluation of new modalities of treatment.