Neonatal Polycythemia May be Free of JAK2V617F Mutation

Abstract

A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Polycythemia is known as increased erythrocytosis and is linked to the erythropoiesis cascade including erythropoietin, erythropoietin receptor and intracellular signaling proteins. The Janus kinase 2 (JAK2) is the key signal transducer in the erythropoiesis cascade. A function gain mutation (V617F) at JAK2 gene has been identified in polycythemia vera in adults. On the other hand, the molecular etiology of neonatal polycythemia has not been elucidated well. Thus, the aim of this randomized controlled study was to investigate the role of JAK2 V617F mutation in the etiology of neonatal polycythemia similar to polycythemia vera. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Fifty-one neonates diagnosed with polycythemia according to venous hematocrit level over 65% and 26 healthy neonates as the control group were enrolled in the study in addition to 43 adult patients diagnosed with polycythemia vera. JAK2 V617F mutation analysis was performed using Real-Time PCR system. R Re es su ul lt ts s: : All the neonatal polycythemia patients were negative for the specific mutation JAK2 V617F, as well as 26 control neonates, whereas in 31 (72%) out of 43 adult polycythemia vera patients, JAK2 V617F mutation was present. C Co on nc cl lu us si io on n: : This is the first report showing that JAK2-V617F mutation may be an acquired somatic mutation instead of congenital and neonatal polycythemia is not related to the disrupted erythropoiesis cascade.K Ke ey y W Wo or rd ds s: : Polycythemia; polycythemia vera; janus kinase 2; infant, newborn; mutation Ö ÖZ ZE ET T A Am ma aç ç: : Polisitemi artmış eritrositoz olarak bilinmektedir ve eritropoetin, eritropoetin reseptörü ve hücre içi sinyal proteinlerini kapsayan eritropoez zinciri ile bağlantılıdır. Janus kinaz 2 (JAK2), eritropoez zincirindeki anahtar sinyal iletim proteini olup, eritropoezin tek hücre içi kinaz proteinidir. Erişkinlerde görülen polisitemi vera hastalığının moleküler zemininde JAK2 geninde bir fonksiyon kazanım mutasyonu olan v617f tanımlanmıştır. Diğer taraftan, yenidoğan polisitemisinin moleküler etiyolojisi çok iyi aydınlatılamamıştır. Bu randomize kontrollü çalışmanın amacı, polisitemi verada olduğu gibi Janus Kinaz 2 (JAK2) V617F mutasyonunun yenidoğan polisitemisinin de etyolojisinde etken olup olmadığını araştırmaktır. G Ge er re eç ç v ve e Y Yö ön n--t te em ml le er r: : Venöz hematokrit düzeyi %65'in üzerinde olmasına göre polisitemi tanısı konulan 51 yenidoğan hasta ile kontrol grubu olarak 26 sağlıklı yenidoğan çocuk çalışılmıştır. Ek olarak, polisitemi vera tanısı almış 43 erişkin hasta çalışmaya dahil edilmiştir. JAK2 V617F mutasyon analizi gerçek zamanlı polimeraz zincir reaksiyonu yöntemi ile yapılmıştır. B Bu ul lg gu ul la ar r: : Yenidoğan polisitemisi olan 51 hasta, kontrol grubundaki 26 yenidoğana benzer şekilde, özgül JAK2 V617F mutasyonu açısından negatif bulundu. Ancak, 43 erişkin polisitemi vera hastasından 31 (%72)'inde JAK2 V617F mutasyonu tespit edildi. S So on ...

The Thrombotic Events in Polycythemia Vera Patients May Be Related to Increased Oxidative Stress

“…However, a few studies suggest that JAK2V617F mutation may not be the initiator of the disease [ 20 ]. It is considered to be a late genetic event occurring in patients with myeloproliferative disease, as reported in our recent studies [ 21 , 22 , 23 ]. The role played by free radicals in causing DNA damage and the pathways of cellular oxidative damage in neoplastic transformation have been well defined [ 24 ].…”

Lentiginoses in polycythemia vera patient: Is there a role forJAK2 (V617F)mutation?

“…Polycythemia Vera, presented in our patient, is a myeloproliferative disorder of bone marrow that red blood cells are produced in large amounts. PV is seen in older ages particularly under the effect of acquired somatic mutation of JAK2 (V617F) 14,15 that the latter is a diagnostic parameter of the disease. 16 JAK2 is a member of the Janus kinase family of nonreceptor protein tyrosine kinases and has an important role in the cellular development and homeostasis.…”

“…Suggestion of a possible role of JAK2 mutations in lentiginosis syndromes with a single case of a patient with multiple lentigines and concomitant diagnosis of polycythemia vera (PV), might be thought as a 'fatal flaw' in the first encounter since JAK2 activating mutations such as V617F in PV are not germline mutations, 14 but rather somatic ones -which supposed to occur only in myeloid haematopoietic progenitors/stem cells; 25 however in our case, surprisingly the cells comprising the skin lentigines of the reported patient do carry the JAK2V617F mutation (Fig. 5).…”

Effect of Polycythemia on Serum Lipid Profile and Oxidative Stress

“…It was found that there is a mutation that causes;true polycythemia vera disease, which occurs in a gene called (The Janus kinasez "JAK" 2),in exon 14 of chromosome 9, and this mutation was;discovered in approximately 95% of patients with .polycythemia vera and about 50% of people with Essential thrombocytosis and primary; myelofibrosis (2) .…”

“…Polycythemia is a Greek term synonymous with Erythrocytosis,and literally translates to many cells in the blood (2) . Polycythemia is an uncommon clinical discovery, and one of its most important features is an increase in the number of red blood cells, as well as an increase in the concentration of hemoglobin (Hb) .and packed cell volume (PCV) (3,4) .…”