Absence of JAK2V617F mutation in patients with beta-thalassemia major and thrombocytosis due to splenectomy

Abstract

The report of Janus Kinase 2 (JAK2) mutations in myeloid malignancies with high frequency in myeloproliferative neoplasms has been well known since 2005. By monitoring allele burden, it is found that the expression of JAK2V617F mutation is increasing significantly from essential thrombocytosis to polycythemia vera. Furthermore, JAK2 abnormalities are reported in the majority of unexplained thrombotic episodes. Thalassemic syndromes are characterized by ineffective erythropoiesis and thrombocytosis, mainly due to splenectomy. The high incidence of thromboembolic events has led to the identification of a prothrombotic state in these patients. The contribution of JAK2 mutations to the hypercoagulable state of thalassemic patients is still unknown. Furthermore, the potential role of Janus Kinase mutations in hepcidin expression and consequently in ineffective erythropoiesis is still under investigation. This study was scheduled to determine whether the presence of JAK2V617F mutation in thalassemic patients is associated with thrombocytosis. We studied 20 patients DNA with beta-thalassemia for JAK2V617F mutation by using RG-PCR method. None of the patients were positive for this particular mutation. More studies are needed to prove the role of JAK2 in ineffective erythropoiesis, iron metabolism and thrombocytosis and to determine if using JAK2 inhibitors in thalassemic patients can be a potential therapeutic option.

Acute Non-Atherosclerotic ST-Segment Elevation Myocardial Infarction in an Adolescent with Concurrent Hemoglobin H-Constant Spring Disease and Polycythemia Vera

“…11 JAK2 mutation analysis is also helpful when investigating MPN since it is mainly positive in MPN, 1 , 11 but absent in thalassemia major patients with thrombocytosis due to splenectomy. 13 This case report illustrates the serious thrombotic complications of PV found in a splenectomized thalassemic patient. Acute myocardial infarction events were reported in both PV and beta-thalassemia major.…”

Polycythemia Vera in a Patient With Heterozygous Beta-Thalassemia: Coincidence or Causal Relationship?

“…It can be postulated that higher levels of Epo result in increased stimulation of the EpoR/JAK2/STAT5 signaling pathway, thus increasing the probability of JAK2 mutations occurring as a result of increased transcriptional activity of the JAK2 gene. [11]. At variance with these negative results, Asadi et al have recently detected this mutation in 19% of 75 patients with beta-thalassemia major [12].…”

Polycythemia vera in patients of beta-thalassemia trait and stress erythropoiesis

“…There is a high turnover of red blood cells behaving under stress in an erythropoiesis-like situation[ 3 , 4 ] There have been some case studies showing an association between beta thalassemia and PV. [ 5 ] The review of the literature showing cases of beta-thalassemia trait with PV are shown in Table 1 [ 1 , 6 7 8 9 10 ] It is possible that chronic stress erythropoiesis which is associated with beta thalassemia can lead to ineffective erythropoiesis and also increase the risk of somatic JAK2 mutation. [ 1 , 5 ] More prospectives are needed to find out the correlation between thalassemia trait and PV.…”