JAK2V617F mutation in patients with β-thalassemia disease: prevalence and clinical characteristics

Teawtrakul, Nattiya; Chansai, Siriyakorn; Yamsri, Supawadee; Ungarreevittaya, Piti

doi:10.1007/s00277-021-04582-0

Cited by 3 publications

(2 citation statements)

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“…Several studies also have provided evidences on the role of JAK2 as a potential target to treat disorders of ineffective erythropoiesis. 74,75 Another studies in mouse models of β-thalassaemia major and intermedia indicated that a short treatment with a JAK2 inhibitor (fedratinib, ruxolitinib [INCB018424;…”

Section: Janus Kinase-2 Inhibitorsmentioning

confidence: 99%

“…The finding of a point mutation in JAK2 at position 617 (valine to phenylalanine, V617F) in the majority of patients with myeloproliferative neoplasms boosted interest in JAK2 inhibitors for the treatment of myeloproliferative neoplasms. Several studies also have provided evidences on the role of JAK2 as a potential target to treat disorders of ineffective erythropoiesis 74,75 . Another studies in mouse models of β‐thalassaemia major and intermedia indicated that a short treatment with a JAK2 inhibitor (fedratinib, ruxolitinib [INCB018424; INC424]) can ameliorate IE and decrease spleen size (Figure 5).…”

Section: Treatment Recommendations Beyond Transfusion and Iron Chelat...mentioning

confidence: 99%

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Beta‐thalassemia and the advent of new interventions beyond transfusion and iron chelation

Chauhan

Shoaib

Fatma

et al. 2022

Brit J Clinical Pharma

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Beta-thalassaemia, including sickle cell anaemia and thalassaemia E, is most common in developing countries in tropical and subtropic regions. Because carriers have migrated there owing to demographic migration, β-thalassaemia can now be detected in areas other than malaria-endemic areas. Every year, an estimated 300 000-500 000 infants, the vast majority of whom are from developing countries, are born with a severe haemoglobin anomaly. Currently, some basic techniques, which include iron chelation therapy, hydroxyurea, blood transfusion, splenectomy and haematopoietic stem cell transplantation, are being used to manage thalassaemia patients. Despite being the backbone of treatment, traditional techniques have several drawbacks and limitations. Ineffective erythropoiesis, correction of globin chain imbalance and adjustment of iron metabolism are some of the innovative treatment methods that have been developed in the care of thalassaemia patients in recent years. Moreover, regulating the expression of B-cell lymphoma/leukaemia 11A and sex-determining region Y-box through the enhanced expression of micro RNAs can also be considered putative targets for managing haemoglobinopathies. This review focuses on the biological basis of β-globin gene production, the pathophysiology of β-thalassaemia and the treatment options that have recently been introduced.

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Section: Janus Kinase-2 Inhibitorsmentioning

confidence: 99%

Section: Treatment Recommendations Beyond Transfusion and Iron Chelat...mentioning

confidence: 99%

Beta‐thalassemia and the advent of new interventions beyond transfusion and iron chelation

Chauhan

Shoaib

Fatma

et al. 2022

Brit J Clinical Pharma

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Ruxolitinib

2021

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Tuberculosis lymphadenitis: case reportIn a study of 170 patients with thalassemia, a man [age not stated] was described, who developed tuberculosis lymphadenitis during treatment with ruxolitinib for primary myelofbrosis with compound heterozygous Hb E-β 0 -thalassemia disease and Hb Pakse (PS).The man, who had had JAK2V617F mutation was diagnosed with primary myelofbrosis with compound heterozygous Hb Eβ 0 -thalassemia disease and Hb PS, received oral ruxolitinib (JAK2 inhibitor) 20mg twice daily. Subsequently, ruxolitinib showed significant clinical improvement. Also, 50% spleen size reduction was observed after 6 months of treatment. However, after one year of treatment, he developed tuberculosis lymphadenitis because of off-target effect of ruxolitinib on immune system.The man received unspecified first-line anti-TB agents and tuberculous lymphadenitis was successfully improved.

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In Silico Multiscale Drug Design to Discover Key Structural Features of Potential JAK2 Inhibitors

et al. 2022

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Background: JAK2 inhibitors have been proposed as a new therapeutic option for thalassemia therapy. The objective of this study was to discover the key structural features for improving 2-aminopyrimidine derivatives as potential JAK2 inhibitors. Materials & methods: Quantitative structure–activity relationship (QSAR) approaches (hologram QSAR and comparative molecular similarity indices analysis), molecular dynamics simulations, binding energy calculations and pharmacokinetic predictions were employed. Results: Reliable QSAR models, binding mode and binding interactions of JAK2 inhibitors were obtained and these obtained results were used as the key information for rational design of highly potent JAK2 inhibitors. Conclusion: The concept of new potential JAK2 inhibitors integrated from the obtained results was proved, producing two newly designed compounds, D01 and D02, with potential for use as JAK2 inhibitors.

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JAK2V617F mutation in patients with β-thalassemia disease: prevalence and clinical characteristics

Cited by 3 publications

References 10 publications

Beta‐thalassemia and the advent of new interventions beyond transfusion and iron chelation

Beta‐thalassemia and the advent of new interventions beyond transfusion and iron chelation

Ruxolitinib

In Silico Multiscale Drug Design to Discover Key Structural Features of Potential JAK2 Inhibitors

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