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Although it is well known that myeloproliferative neoplasms occur in younger patients, few large cohorts of such patients have been reported. Thus, our knowledge about circumstances of diagnosis, outcome and treatment is limited, especially for children and young adults. We therefore performed a systematic review of cases, published since 2005, concerning patients aged below 20 years at the time of diagnosis of essential thrombocythemia or polycythemia vera. We identified 396 cases of essential thrombocythemia and 75 of polycythemia vera. The median age at diagnosis was 9.3 and 12 years, respectively, and females constituted 57.6% and 45% of the groups, respectively. Half of the patients were asymptomatic at diagnosis. The proportion of so-called triple negativity was high: 57% in essential thrombocythemia and 73% in polycythemia vera. The incidence of thrombosis during the follow-up was 9.3% in patients with polycythemia vera and less, 3.8%, in those with essential thrombocythemia. Venous events were predominant (84.2%), with hemorrhagic episodes being rarer (<5%). The risk of evolution also seemed low (2% to myelofibrosis and no reports of acute leukemia), but the median follow-up was only 50 months. Survival curves were not available. Half of the patients received an antithrombotic drug and 40.5% received a cytoreductive drug. All data should be analyzed with care because of the proportion of missing data (10.7% to 74.7%). This review highlights interesting points concerning this population of young patients with myeloproliferative neoplasms, including that such patients were identified as negative for all common driver mutations, but also shows the need for larger contemporary cohorts with longer follow-up to assess the true prognosis of these patients., (Copyright© 2019 Ferrata Storti Foundation.)

Cytokines are essential regulators of hematopoiesis, acting in an instructive or permissive way. Fms-like tyrosine kinase 3 ligand (FLT3L) is an important cytokine for the development of several hematopoietic populations. Its receptor (FLT3) is expressed on both myeloid and lymphoid progenitors and deletion of either the receptor or its ligand leads to defective developmental potential of hematopoietic progenitors. In vivo administration of FLT3L promotes expansion of progenitors with combined myeloid and lymphoid potential. To investigate further the role of this cytokine in hematopoietic development, we generated transgenic mice expressing high levels of human FLT3L. These transgenic mice displayed a dramatic expansion of dendritic and myeloid cells, leading to splenomegaly and blood leukocytosis. Bone marrow myeloid and lymphoid progenitors were significantly increased in numbers but retained their developmental potential. Furthermore, the transgenic mice developed anemia together with a reduction in platelet numbers. FLT3L was shown to rapidly reduce the earliest erythroid progenitors when injected into wild-type mice, indicating a direct negative role of the cytokine on erythropoiesis. We conclude that FLT3L acts on multipotent progenitors in an instructive way, inducing their development into myeloid/lymphoid lineages while suppressing their megakaryocyte/erythrocyte potential.

Unlabelled: Background The MPL(Ser505Asn) mutation has been reported to be a cause of hereditary thrombocythemia. Recently, we detected this mutation in a large proportion of children with familial thrombocythemia, suggesting that in Italy the incidence of MPL(Ser505Asn) mutation could be underestimated., Design and Methods: We extended the search for this mutation to all patients with essential thrombocythemia who had a positive family history for thrombocytosis or essential thrombocythemia. We identified eight Italian families positive for the MPL(Ser505Asn) mutation. Clinical and hematologic data were available for members of seven families, including 21 patients with a proven mutation and 20 relatives with thrombocytosis., Results: Fifteen major thrombotic episodes, nine of which were fatal, were recorded among 41 patients. The thrombotic manifestation was stroke in four cases, myocardial infarction in seven cases, fetal loss in two cases, deep vein thrombosis of the leg in one case and Budd Chiari syndrome in one case. Almost all patients over 20 years old had splenomegaly and bone marrow fibrosis, while these were rarely observed in patients under 20 years old, suggesting that these manifestations are associated with aging. Finally, the life expectancy of family members with thrombocytosis was significantly shorter than that of members without thrombocytosis (P=0.003). Conclusions Patients with familial thrombocytosis caused by a MPL(Ser505Asn) mutation have a high risk of thrombosis and, with aging, develop splenomegaly and bone marrow fibrosis, significantly affecting their life expectancy.