Poster Session I: Myeloproliferative neoplasms - Biology & translational research
Absolute erythrocytosis is characterized by persistently raised Haemoglobin (Hb) and hematocrit (Ht) levels. The most studied form is Polycythemia Vera (PV), a clonal disease in which the proliferation of red cells is driven by mutations in JAK2. Secondary erythrocytosis are represented by rare congenital diseases, acquired forms, or idiopathic erythrocytosis (IE), a poorer studied disease in which the erythrocytosis has not a definite cause. Over-production of red blood cells should drive a depletion of iron, and thus low serum ferritin levels. However, we often observe increased levels of ferritin at diagnosis in IE and we recently found that mutations or polymorphisms of HFE gene are commonly found in these patients.
Could serum ferritin be an early help to hypothesize the cause of erythrocytosis in a patient? To answer this question, we retrospectively analysed levels of ferritin at diagnosis in PV and IE patients.
We studied 72 patients with PV and 67 patients with IE, followed in our department. In each patient we recorded ferritin at diagnosis out of phlebotomy treatment. Other causes of hypo- and hyper- ferritinemia were excluded. Ferritin normal levels were considered 20-300 μg/L in men and 15-200 μg/L in women. All patients with a diagnosis of PV carried JAK2V617F or JAK 2 exon 12 mutation, while none of the patients with IE carried JAK2 or EPOR, VHL, PHD2, HIF-1 alpha genes mutations. Presence and absence of HFE mutations in IE patients, if known, were registered. Statistical analysis was performed using the Mann-Whitney test, Fisher's exact test and the t Student test.
Results are shown in the Table I.
In addition, HFE mutations had been searched in 26 (39%) IE patients, and 13 (50%) of them had at least a mutated allele.
Our results show a dramatic difference between levels of ferritin at diagnosis in PV and IE: in fact, 22% of PV patients had reduced ferritin at diagnosis out of phlebotomies, while on the contrary 28% of IE patients had increased levels of ferritin. Then, serum ferritin at diagnosis could address the physician to the origin of erythrocytosis. In addition, nearly half of IE patients have been already studied for presence of HFE mutations, and half of them carry at least one HFE mutated allele. We believe that a large part of IE patients carries a genetic impairment of the iron metabolism that could drive an enhancement of iron production: this could explain why in the presence of erythrocytosis iron is more consumed in PV patients than in IE ones. Further studies are needed about the presence of iron metabolism impairments in IE patients and, on the other hand, possible overlays of JAK2 and HFE mutations in PV patients.