Sideroblastic Anemias Associated with Marked Thrombocytosis, the Role of JAK2 (V616F) Mutation (exon 6 and 12)

Abstract 5135

The refractory anemia with ringed sideroblasts (RARS) and multilineage dysplasia is often associated with marked thrombocytosis; the research of JAK2 (V617F) mutant alleles was positive, JAK2 mutation is present in patients with polycythaemia vera (70%-95%), essential throbocythemia (32%-58%), CIMF (36%-50%), resulting in a valine to phenylalanine substitution at position 617; the mutation increases the kinase activity of JAK2 and the auto-phosphorylation and hyperactivation of EPOR and TPOR these two causing eritroid cells hyperplasia, the increase of dysgranulocytopoiesis with small hypolobulated dysplastic form and megakaryocytopoiesis with cluster of giant cells and enhanced risk for thrombosis greater than 30% or recurrent thrombosis greater than 20%. Dysgranulocytopoiesis features includes hypogranulation of myeloid cells, pseudo Pelger form, ringed sideroblastosis, thrombocytosis (>600.000/nL) with refractory cytopenia, and signficantly higher levels of PF4.

We have studied 8 patients with RARS–T, and we have found that JAK2 mutation is present in 5 out of 8 patients; these patients had a significantly higher white cells count, an increase of the tyrosin-kinase 2, and an enhanced activation of downstream transcription factors such as STAT-3 and STAT-5 A/B signalling cytokines that induce FOXP3 up regulation in activated CD4+, CD25+ regulatory T cells. Several defects of aggregation are present and deficiency of ATIII, PC, PS, splenomegaly were associated with a mild bleeding tendency.