Background: Chronic Myeloproliferative Neoplasms (MPN) are clonal diseases of middle-advanced age while they are extremely rare in pediatric patients.JAK2V617F mutation is the main molecular marker of MPN, occurring in the great majority of patients: 95% of patients with polycythemia vera (PV) and 50-60% of those with essential thrombocythemia (ET)andmyelofibrosis (PMF).The rare cases of children with MPN seem to have different biological characteristics in comparison to adult MPN, but few data are published on this subject. Aims: In this study, we report our experience in a large cohort of pediatric patients with high platelet count in whom JAK2V617F and MPLmutations have been searched. Methods: We report 86 children with sustained thrombocytosis (>600 x 109/L) over at least 6 months, in the absence of recognizable reactive or secondary cause, followed in one of the Centers linked to the Italian Pediatric Hemato-Oncology Association. There was no family history of MPN. The genotyping of the JAK2V617F mutation was performed by allele-specific PCR and the mutant allele-burden was measured by quantitative real time-polymerase chain reaction assay.MPLmutations were searched by direct sequencing. Clonality was studied on females according to HUMARA method.Differences in the distribution of continuous variables between categories were analyzed by the Mann-Whitney test. Results: JAK2V617F mutation was found in 11 (13.4%) patients (allele burden 26.26±9.78%).Mutations in the MPL gene were searched in 57 patients with thrombocytosis and one (1.7%) had a somatic mutation (W515L). Clonality was available in 21 females and 6 of them (26.5%) resulted monoclonal (2 carrying JAK2 mutation). On a whole 18.6% of patients had a clonal disease, while other 74 patients had a thrombocytosis of undefined origin. In the table the hematological data of the patients are summarized. Image / Pictures: Summary / Conclusion: Our data confirm that clonal ET is rarely found even in children with sustained, prolonged thrombocytosis without any recognizable cause. No significant hematological difference was observed between patients with a sure MPN and those with an undefined thrombocytosis. JAK2V617F mutation is uncommon and other mutations such as MPLW515L are anecdotal. If clonal ET in pediatrics would represent 50-60% of all ET as it is in adults, then additional 40% of children would be found within our series, their number adding at the most to 10 children. Therefore, all other studied patients could be ???undefined thrombocytosis??? and their diagnostic process and follow-up need to be further established.

HOW MANY CHILDREN WITH THROMBOCYTOSIS OF UNDEFINED ORIGIN HAVE A MYELOPROLIFERATIVE NEOPLASM?

RANDI, MARIA LUIGIA;GERANIO, GIULIA;BASSO, GIUSEPPE;FABRIS, FABRIZIO
2013

Abstract

Background: Chronic Myeloproliferative Neoplasms (MPN) are clonal diseases of middle-advanced age while they are extremely rare in pediatric patients.JAK2V617F mutation is the main molecular marker of MPN, occurring in the great majority of patients: 95% of patients with polycythemia vera (PV) and 50-60% of those with essential thrombocythemia (ET)andmyelofibrosis (PMF).The rare cases of children with MPN seem to have different biological characteristics in comparison to adult MPN, but few data are published on this subject. Aims: In this study, we report our experience in a large cohort of pediatric patients with high platelet count in whom JAK2V617F and MPLmutations have been searched. Methods: We report 86 children with sustained thrombocytosis (>600 x 109/L) over at least 6 months, in the absence of recognizable reactive or secondary cause, followed in one of the Centers linked to the Italian Pediatric Hemato-Oncology Association. There was no family history of MPN. The genotyping of the JAK2V617F mutation was performed by allele-specific PCR and the mutant allele-burden was measured by quantitative real time-polymerase chain reaction assay.MPLmutations were searched by direct sequencing. Clonality was studied on females according to HUMARA method.Differences in the distribution of continuous variables between categories were analyzed by the Mann-Whitney test. Results: JAK2V617F mutation was found in 11 (13.4%) patients (allele burden 26.26±9.78%).Mutations in the MPL gene were searched in 57 patients with thrombocytosis and one (1.7%) had a somatic mutation (W515L). Clonality was available in 21 females and 6 of them (26.5%) resulted monoclonal (2 carrying JAK2 mutation). On a whole 18.6% of patients had a clonal disease, while other 74 patients had a thrombocytosis of undefined origin. In the table the hematological data of the patients are summarized. Image / Pictures: Summary / Conclusion: Our data confirm that clonal ET is rarely found even in children with sustained, prolonged thrombocytosis without any recognizable cause. No significant hematological difference was observed between patients with a sure MPN and those with an undefined thrombocytosis. JAK2V617F mutation is uncommon and other mutations such as MPLW515L are anecdotal. If clonal ET in pediatrics would represent 50-60% of all ET as it is in adults, then additional 40% of children would be found within our series, their number adding at the most to 10 children. Therefore, all other studied patients could be ???undefined thrombocytosis??? and their diagnostic process and follow-up need to be further established.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/3041316
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