Abstract

Chronic myeloproliferative syndromes (MPS) are clonal stem cell disorders resulting in excessive proliferation of one or more cell lineages. Rare families exist with first-degree relatives affected by MPS. Familial or hereditary essential thrombocythemia (HT) is described among children with primary thrombocytosis and it is inherited in an autosomal-dominant manner. In HT germ-line activating mutations of thrombopoietin (TPO) gene or its receptor, c-MPL can be recovered. A 31-year-old woman was first referred to our Clinic for an isolated high platelet count. On routine blood testing performed when she was 14 years old the platelet count was 1020 × 103/μl; at that time she refused other laboratory examinations, instrumental and histological diagnostic procedures and subsequent therapy and she remained asymptomatic. During the first pregnancy the platelet count went down to 500 × 103/μl but after the second it raised over one million per microliter. Bone marrow trephine biopsy showed clusters of megakaryocytes with hyperlobulated forms and platelet clumps; the caryotype was normal and bcr-abl rearrangements were negative. Leukocytic alkaline phosphatase was high, there was reduced platelet aggregation, the thrombophilic study didn’t demonstrate either factor V Leiden G1691A or prothrombin Gene G20210A mutations. During the follow up the platelet count remained under 1000 × 103/μl so that a watch-and-wait strategy seemed appropriate in this asymptomatic case and low-dose aspirin has been started. What is remarkable in this case is that it is a not-frequent example of HT since the patient’s father, sister and niece are all affected by essential thrombocytemia (ET); moreover the patient’s own little daughter is affected by neonatal thrombocytosis. The relatives are being treated only with low-dose aspirin, they are completely asymptomatic without thrombohemorrhagic events. Some authors report that HT appears to be a different disease from sporadic ET and with a more benign course. The somatic activating point mutation (V617F) in the JAK2 gene was not demonstrated in our patient; as for TPO and c-MPL mutations we are now completing the genetic study. Among other familiar chronic MPS we describe the occurrence of ET/PV and idiopathic myelofibrosis (IMF) in two monozygotic twin sisters. They both were diagnosed with MPS at the median age of 65 years old. The first had splenomegaly, thrombocytosis and erythrocytosis and was treated with aspirin, hydroxyurea and phlebotomy. The other, affected by IMF, had important epato-splenomegaly and the bone marrow trephine biopsy showed myelofibrosis with >90% collagen fibres. She received low dose hydroxyurea together with nandrolone decanoate; the organomegaly reduced and the hematic crasis improved. The JAK2 gene mutation was demonstrated only in the IMF patient. This second familial case strengthens the concept of a common pathogenesis of chronic MPS and suggests a genetic and hereditary etiology; moreover the occurrence of multiple disease phenotypes in a family is consistent with the theory of MPS as arising from clonal expansion of a pluripotential haematopoietic precursor cell that retains its pluripotentiality and produces an array of inter-related syndromes.

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