PROGNOSTIC VALUE OF C-MPL EXPRESSION IN MYELODYSPLASTIC SYNDROMES

The c-mpl proto oncogene which encodes a member of the hematopoietic c ytokine receptor superfamily has been recently shown to be the recepto r for thrombopoietin (TPO), which stimulates megakaryocyte progenitor expansion and differentiation. We studied c-mpl expression by Northern blot analysis, in a large series of 58 MDS. No expression was found i n 14 patients with refractory anemia (RA) or with refractory anemia wi th ring sideroblasts (RARS). In contrast 11/26 (42%) patients with ref ractory anemia with excess of blasts (RAEB), or with RAEB in transform ation (RAEBt), and 8/18 (44%) patients with chronic myelomonocytic leu kemia (CMML) expressed c-mpl. In CMML patients, no correlation was fou nd between c-mpl expression and any prognostic factor tested, nor with the course of the disease. In contrast, in RAEB and RAEBt, expression of c-mpl was correlated with high Bournemouth scoring (P < 0.005) and poor survival (P = 0.02) due to leukemic transformation. Forty-five p er cent (5/11) of the c-mpl positive patients evolved towards AML with a mean follow-up of 10.5 months, while 13% (2/15) of the c-mpl negati ve patients developed a secondary leukemia, with a mean follow-up of 2 1.1 months, Moreover, in RAEB and RAEBt, a significant correlation was observed between c-mpl, CD34, megakaryocyte glycoprotein Ilb (GPIIb) expression, acid the presence of dysmegakaryopoiesis. These results in dicate that patients with RAEB and RAEBt, with high expression of the c-mpl, CD34, and GPIIb genes, may identify a subgroup of patients with particularly poor prognosis, due to an increased risk of secondary le ukemia. More aggressive therapy could be justified in these patients.