Frequency and clinical features of the <i>JAK2</i> V617F mutation in pediatric patients with sporadic essential thrombocythemia

Nakatani, Takuya; Imamura, Toshihiko; Ishida, Hiroyuki; Wakaizumi, Katsuji; Yamamoto, Tohru; Otabe, Osamu; Ishigami, Tatsuzo; Adachi, Souichi; Morimoto, Akira

doi:10.1002/pbc.21730

Cited by 12 publications

(9 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The acquired JAK2 V617F mutation, resulting in constitutive activation of tyrosine kinases in the absence of cytokines, is present in around 50–60% of adult ET patients (Baxter et al , ). Varying frequencies of the JAK2 V617F mutation have been reported in childhood ET, ranging from 0% to 50%, lower than or similar to that in adults (Randi et al , ; El‐Moneim et al , ; Teofili et al , ,b; Nakatani et al , ; Veselovska et al , ; Giona et al , ; Ismael et al , ) (Table ). The variability can probably be ascribed to the heterogeneity of each cohort, as remarkably different frequencies have been detected using the same method to identify the JAK2 mutation (Randi et al , ; Teofili et al , ; Giona et al , ).…”

Section: Molecular Features and Clonal Evolutionmentioning

confidence: 98%

“…Children diagnosed with ET are reported to have a lower risk of vascular events than adults. The rate of thrombotic events in children is 0-11Á1%, and major bleeding events are rarely seen (Yang & Qian, 2000;Randi et al, 2006;Teofili et al, 2007aTeofili et al, , 2009Nakatani et al, 2008;Veselovska et al, 2008;Giona et al, 2012) (Table I). After a long period of follow-up, Teofili et al (2007aTeofili et al ( , 2009 reported that the risk of thrombotic events from two paediatric ET cohorts was 0/18 (0%) and 1/13 (7Á7%), respectively, both much lower than that of adult patients (31%).…”

Section: Clinical Manifestation and Complicationsmentioning

confidence: 99%

See 1 more Smart Citation

Paediatric essential thrombocythaemia: clinical and molecular features, diagnosis and treatment

Zhang

Yang

2013

Br J Haematol

View full text Add to dashboard Cite

SummaryThe incidence of essential thrombocythaemia (ET) in children (age ≤18 years) is extremely low. The natural course of the disorder in children has not been clarified. The rarity of patients and the variability of tested parameters make it difficult to draw any definitive conclusion in pathogenesis and diagnosis of paediatric ET. What makes the onset of thrombocytosis earlier in children is still uncertain. A diagnostic algorithm for paediatric ET has not been established, and current risk stratification used to guide therapeutic decisions in adults has not been validated in children. Vascular complications and transformation to myelofibrosis and leukaemia in this special entity have been reported, suggesting that ET in children is not an entirely benign disease. The crucial question is how to identify patients who are at high risk of complications and need treatment. There are insufficient data to recommend a specific agent in children. The purpose of this review is to outline the most recent progress in paediatric ET and to help with understanding the clinical course, molecular features, diagnosis and treatment strategies in this special group.

show abstract

Section: Molecular Features and Clonal Evolutionmentioning

confidence: 98%

Section: Clinical Manifestation and Complicationsmentioning

confidence: 99%

Paediatric essential thrombocythaemia: clinical and molecular features, diagnosis and treatment

Zhang

Yang

2013

Br J Haematol

View full text Add to dashboard Cite

show abstract

“…Diagnosis of ET in children may require exclusion of hereditary manifestations transmitted as hereditary character, involving genetic defects of thrombopoietin receptor, thrombopoietin and MPL mutations expressed in both somatic and germ line cells. 7 Primary myelofibrosis The proposed 2008 WHO criteria for PMF are applicable in children and young adults. Bone marrow histology is essential to exclude secondary causes of myelofibrosis (neoplastic and non-neoplastic) and the prefibrotic phase of PMF that presents a different natural history in comparison with true ET.…”

Section: How To Diagnose Mpn In Children and Young Adultsmentioning

confidence: 99%

How to manage children and young adults with myeloproliferative neoplasms

Barbui

2012

Leukemia

View full text Add to dashboard Cite

On the basis of my personal clinical and research experience and validated by the current literature, my approach to the management of pediatric (age o18 years) and young patients (age o40 years) with classic myeloproliferative neoplasms is presented by focusing on diagnosis, patient communication, risk stratification and therapy. The WHO-2008 diagnostic criteria are recommended, even though in children suspected with essential thrombocythemia (ET), a specific set of diagnostic features may be required. Patient communication includes information on natural history, genetic abnormalities and counseling in all women of child-bearing age. The main challenge in children and young adults with ET and polycythemia vera (PV) is to avoid recurrence of major thrombosis by selecting those patients who ultimately can benefit from cytotoxic and antithrombotic therapy without increasing the incidence of drug-induced side effects. In asymptomatic low-risk patients no therapy is prescribed while in high-risk low-dose aspirin, hydroxyurea and interferon-alpha are my first line drugs. My first decision when considering treatment of a young patient with primary myelofibrosis (PMF) or post-PV or post ET-myelofibrosis, is whether he/she qualifies for bone marrow allotransplantation. In the remaining young PMF patients palliative therapy or experimental drugs are considered.Leukemia ( Keywords: myeloproliferative neoplasms; treatment; young people INTRODUCTION Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are currently classified among the bcr/abl-negative, 'classic' myeloproliferative neoplasms (MPNs) and represent a stem cell-derived clonal myeloproliferation. Hematopoietic progenitors derived from patients with MPNs are hypersensitive to the stimulation of physiological growth factors such as thrombopoietin or erythropoietin (EPO). 1 Since 2005, the pathophysiology of these diseases has advanced considerably with the discovery of an acquired mutation of JAK2 V617F in a vast majority of PV patients and in almost half of those with ET and PMF. 2 The mutation, located within the negative regulatory pseudokinase, or Janus homology 2 domain, causes cytokine-independent activation of several biochemical pathways implicated in EPO receptor signaling. Subsequently, mutations in MPL were reported in B4% of patients with ET or PMF. The significance of JAK2 and MPL mutations for the evolution of the MPNs and their relative roles in determining disease phenotype as well as progression to myelofibrosis and leukemic transformation are unclear at present.In this context, it should be underscored that most of the information in terms of diagnosis, prognosis and therapy focuses on the 'average' MPN patients of whom median age ranges between 60 and 65 years. On the other hand, less consistent data are available in the groups of MPN patients who are presenting below this median age such as pediatric and young adults (20% of MPN patients). This issue is now becoming more and more important, because with the ad...

show abstract

“…One small study showed that 3 of 6 pediatric ET patients harbored a JAK2V617F mutation, but all had increased PRV-1 expression. 62 A larger study showed a significantly decreased frequency of JAK2V617F mutation in pediatric patients compared to adults. It also showed a significantly lower degree of clonality in the pediatric patients.…”

mentioning

confidence: 97%

Primary thrombocytosis in children

et al. 2014

View full text Add to dashboard Cite

Myeloproliferative neoplasms are uncommon disorders in children, for which we have limited understanding of the pathogenesis and optimal management. JAK2 and MPL mutations, while common drivers of myeloproliferative neoplasms in adult patients, are not clearly linked to pediatric disease. Management and clinical outcomes in adults have been well delineated with defined recommendations for risk stratification and treatment. This is not the case for pediatric patients, for whom there is neither a standard approach to workup nor any consensus regarding management. This review will discuss thrombocytosis in children, including causes of thrombocytosis in children, the limited knowledge we have regarding pediatric primary thrombocytosis, and our thoughts on potential risk stratification and management, and future questions to be answered by laboratory research and collaborative clinical study. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o ngenerally on control at the transcriptional level. 13 This rate depends upon TPO binding to its receptor, which in turn depends upon how many TPO-R bearing cells are accessible, as well as how many receptors they express.14 Low platelet counts will lead to decreased TPO clearance (less receptors in the circulation) and therefore increased levels of TPO; the reverse occurs with higher platelet counts, i.e. thrombocytosis. There are variations to this basic principal, for example in the setting of idiopathic thrombocytopenia (thrombocytopenia due to destruction). In these cases, the number of megakaryocytes and megakaryocyte mass may also influence TPO regulation and circulating levels. 15,16 Causes of reactive thrombocytosis in childrenSecondary, or reactive, thrombocytosis is a common occurrence in children. It has been reported to occur in 6-15% of hospitalized children, with variations based on age. Most of these children had thrombocytosis that could be characterized as mild, but others transiently reached levels over 900,000. [17][18][19][20] Causes of secondary thrombocytosis are many and varied (Table 1). Infection is the most common, including viral and bacterial pathogens, and both acute and chronic infections. Especially in children under one year of age, any infection seems capable of triggering a high platelet count. Inflammatory diseases, e.g. Kawasaki disease, rheumatoid arthritis, and inflammatory bowel disease, are commonly associated with reactive thrombocytosis, as are hypoxia, trauma, blood loss, and malignancy. 19,21,22 Iron deficiency also seems to be a frequent cause of secondary thrombocytosis. 20 It is believed that underlying mechanisms of secondary thrombocytosis can be explained by upregulation of TPO expression and resultant increased TPO levels. Hepatic TPO mRNA expression is increased with inflammation. Figure 1 shows our groups' proposed diagnostic algorithm for approaching patients with elevated platelets. Evaluation for secondary causes, such as iron deficiency or inflammatory or infectious disorders is conducted. Iron deficiency and othe...

show abstract

Frequency and clinical features of the JAK2 V617F mutation in pediatric patients with sporadic essential thrombocythemia

Abstract: These findings suggest that the JAK2 V617F mutation is not rare in childhood sporadic ET cases, and that these cases might be older and myeloproliferative features.

Cited by 12 publications

References 20 publications

Paediatric essential thrombocythaemia: clinical and molecular features, diagnosis and treatment

Paediatric essential thrombocythaemia: clinical and molecular features, diagnosis and treatment

How to manage children and young adults with myeloproliferative neoplasms

Primary thrombocytosis in children

Contact Info

Product

Resources

About