Prévalence et facteurs prédictifs des mutations JAK2V617F, CALR et MPL dans la thrombose veineuse splanchnique
DOI :
https://doi.org/10.62438/tunismed.v103i6.5682Mots-clés :
JAK2V617F, MPL, CALR, thrombose veineuse splanchnique, néoplasie myéloproliférativeRésumé
Introduction-Objectif: Les néoplasies myéloprolifératives (NMP) latentes ont été rapportés dans les thromboses veineuses splanchniques (TVS). Cette première étude tunisienne a pour objectif d’évaluer la fréquence des mutations JAK2V617F, MPL et CALR dans les TVS et d’analyser leur corrélation avec les paramètres hématologiques.
Méthodes : Cette étude menée entre 2013 et 2017 a inclus les TVS non malignes et non cirrhotiques. Les mutations JAK2V617F et MPL ont été détectée par PCR en temps réel. La mutation CALR a été dépistée par PCR et séquençage direct.
Résultats : La mutation JAK2V617F a été détectée dans 20,1% des 233 cas de TVS avec une prévalence significativement plus élevée dans le syndrome de Budd Chiari (SBC). Les mutations MPL et CALR n'ont pas été détectées. La fréquence de la NMP latente était de 36,2 % dans les TVS, 31,7 % dans les thromboses de la veine porte et de 66,6 % dans le SBC. Les patients atteints de TVS avec un taux d'Hb ≥14,5g/dl pour les hommes, 11,4 g/dl pour les femmes, leucocytes ≥6100/mm3 et plaquettes ≥238000/mm3 pourraient être testés pour la mutation JAK2V617F. Cette stratégie permet d'éviter 89,5 % des tests inutiles chez les patients en dessous de ces seuils. Une numération plaquettaires ≥238000/mm3 était un facteur indépendant corrélé à la mutation JAK2V617Fet un puissant prédicteur d’une NMP latente (OR=17,3 ; 95% CI [2,8-105,1]);p=0,002).
Conclusion : La recherche de JAK2V617F est utile pour diagnostiquer les NMP latentes révélées par une TVS, tandis que MPL et CALR sont rares et non recommandées.
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Références
Valeriani E, Riva N, Di Nisio M et al. Splanchnic Vein Thrombosis: Current Perspectives. Vascular Health and Risk Management. 2019;15:449.
Zhang Y, Zhou Y, Wang Y et al. Thrombosis among 1537 patients with JAK2 V617F -mutated myeloproliferative neoplasms: Risk factors and development of a predictive model. Cancer medicine. 2020;9(6):2096–2105.
Smalberg JH, Arends LR, Valla DC et al. Myeloproliferative neoplasms in Budd-Chiari syndrome and portal vein thrombosis : a meta-analysis. Blood. 2012;120(25):2–4.
Tremblay D, Vogel AS, Moshier E et al. Outcomes of splanchnic vein thrombosis in patients with myeloproliferative neoplasms in a single center experience. European Journal of Haematology. 2020;104(1):72–73.
Sekhar M, Mcvinnie K, Burroughs AK. Splanchnic vein thrombosis in myeloproliferative neoplasms. British Journal of Haematology. 2013;162(6):730–747.
Kiladjian JJ, Cervantes F, Leebeek FWG et al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: A report on 241 cases. Blood. 2008;111(10):4922–4929.
Yonal I, Pinarbası B, Hindilerden F et al. The clinical significance of JAK2V617F mutation for Philadelphia-negative chronic myeloproliferative neoplasms in patients with splanchnic vein thrombosis. Journal of Thrombosis and Thrombolysis. 2012;34(3):388–396.
Amarapurkar D, Punamiya S, Patel N et al. Prevalence of JAK29V617F) mutation in intra-abdominal venous thrombosis. Gastroenterology. 2011;32(4):279–284.
Araki M, Yang Y, Masubuchi N et al. Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms. Blood. 2016;127(10):1307–1316.
Nangalia J, Massie CE, Baxter EJ et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. The New England journal of medicine. 2013;369(25):2391–2405.
Mahjoub S, Baccouche H, Sahnoun M et al. La mutation JAK2 dans les syndromes myéloprolifératifs BCR-ABL négatifs: facteur prédictif de thrombose. Tunis Med. 2015 Jul;93(7):474-7.
Hindilerden F, Hindilerden IY, Pinarbasi B et al. The Clinical Significance of JAK2V617F Mutation for Philadelphia–Negative Chronic Myeloproliferative Neoplasms in Patients with Splanchic Vein Thrombosis. Clinical Lymphoma Myeloma and Leukemia. 2019;19. doi:10.1016/j.clml.2019.07.377.
Sassi H, Menif S, Ammar S Ben, Farrah A. JAK2 p.(V617F) mutation in Tunisian myeloproliferative neoplasms and its genotype-phenotype correlation. PAMJ 2021; 39:194. 2021;39(194). doi:10.11604/PAMJ.2021.39.194.28307.
Sant’Antonio E, Guglielmelli P, Pieri L et al. Splanchnic vein thromboses associated with myeloproliferative neoplasms: An international, retrospective study on 518 cases. American Journal of Hematology. 2020;95(2):156–166.
Primignani M, Barosi G, Bergamaschi G et al. Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis. Hepatology. 2006;44(6):1528–1534.
De Stefano V, Qi X, Betti S et al. Splanchnic vein thrombosis and myeloproliferative neoplasms: molecular-driven diagnosis and long-term treatment. Thrombosis and Haemostasis. 2015;115(2):240–249.
Sekhar M, Mcvinnie K, Burroughs AK. Splanchnic vein thrombosis in myeloproliferative neoplasms. British Journal of Haematology. 2013;162(6):730–747.
Sarid N, Eshel R, Rahamim E et al. JAK2 mutation: An aid in the diagnosis of occult myeloproliferative neoplasms in patients with major intraabdominal vein thrombosis and normal blood counts. Israel Medical Association Journal. 2013;15(11):698–700.
Ageno W, Beyer-Westendorf J, Garcia DA et al. Guidance for the management of venous thrombosis in unusual sites. Journal of Thrombosis and Thrombolysis.41. doi:10.1007/s11239-015-1308-1.
Nerea C, Inmaculada R, Rosa A J et al. Carl mutation screening should not be studied in splanchnic vein thrombosis. British Journal of Haematology. 2015;170(4):586–588.
Valeriani E, Riva N, Di Nisio M et al. Splanchnic Vein Thrombosis: Current Perspectives. Vascular Health and Risk Management. 2019;15:449.
Zhang Y, Zhou Y, Wang Y et al. Thrombosis among 1537 patients with JAK2 V617F -mutated myeloproliferative neoplasms: Risk factors and development of a predictive model. Cancer medicine. 2020;9(6):2096–2105.
Smalberg JH, Arends LR, Valla DC et al. Myeloproliferative neoplasms in Budd-Chiari syndrome and portal vein thrombosis : a meta-analysis. Blood. 2012;120(25):2–4.
Tremblay D, Vogel AS, Moshier E et al. Outcomes of splanchnic vein thrombosis in patients with myeloproliferative neoplasms in a single center experience. European Journal of Haematology. 2020;104(1):72–73.
Sekhar M, Mcvinnie K, Burroughs AK. Splanchnic vein thrombosis in myeloproliferative neoplasms. British Journal of Haematology. 2013;162(6):730–747.
Kiladjian JJ, Cervantes F, Leebeek FWG et al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: A report on 241 cases. Blood. 2008;111(10):4922–4929.
Yonal I, Pinarbası B, Hindilerden F et al. The clinical significance of JAK2V617F mutation for Philadelphia-negative chronic myeloproliferative neoplasms in patients with splanchnic vein thrombosis. Journal of Thrombosis and Thrombolysis. 2012;34(3):388–396.
Amarapurkar D, Punamiya S, Patel N et al. Prevalence of JAK29V617F) mutation in intra-abdominal venous thrombosis. Gastroenterology. 2011;32(4):279–284.
Araki M, Yang Y, Masubuchi N et al. Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms. Blood. 2016;127(10):1307–1316.
Nangalia J, Massie CE, Baxter EJ et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. The New England journal of medicine. 2013;369(25):2391–2405.
Mahjoub S, Baccouche H, Sahnoun M et al. La mutation JAK2 dans les syndromes myéloprolifératifs BCR-ABL négatifs: facteur prédictif de thrombose. Tunis Med. 2015 Jul;93(7):474-7.
Hindilerden F, Hindilerden IY, Pinarbasi B et al. The Clinical Significance of JAK2V617F Mutation for Philadelphia–Negative Chronic Myeloproliferative Neoplasms in Patients with Splanchic Vein Thrombosis. Clinical Lymphoma Myeloma and Leukemia. 2019;19. doi:10.1016/j.clml.2019.07.377.
Sassi H, Menif S, Ammar S Ben, Farrah A. JAK2 p.(V617F) mutation in Tunisian myeloproliferative neoplasms and its genotype-phenotype correlation. PAMJ 2021; 39:194. 2021;39(194). doi:10.11604/PAMJ.2021.39.194.28307.
Sant’Antonio E, Guglielmelli P, Pieri L et al. Splanchnic vein thromboses associated with myeloproliferative neoplasms: An international, retrospective study on 518 cases. American Journal of Hematology. 2020;95(2):156–166.
Primignani M, Barosi G, Bergamaschi G et al. Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis. Hepatology. 2006;44(6):1528–1534.
De Stefano V, Qi X, Betti S et al. Splanchnic vein thrombosis and myeloproliferative neoplasms: molecular-driven diagnosis and long-term treatment. Thrombosis and Haemostasis. 2015;115(2):240–249.
Sekhar M, Mcvinnie K, Burroughs AK. Splanchnic vein thrombosis in myeloproliferative neoplasms. British Journal of Haematology. 2013;162(6):730–747.
Sarid N, Eshel R, Rahamim E et al. JAK2 mutation: An aid in the diagnosis of occult myeloproliferative neoplasms in patients with major intraabdominal vein thrombosis and normal blood counts. Israel Medical Association Journal. 2013;15(11):698–700.
Ageno W, Beyer-Westendorf J, Garcia DA et al. Guidance for the management of venous thrombosis in unusual sites. Journal of Thrombosis and Thrombolysis.41. doi:10.1007/s11239-015-1308-1.
Nerea C, Inmaculada R, Rosa A J et al. Carl mutation screening should not be studied in splanchnic vein thrombosis. British Journal of Haematology. 2015;170(4):586–588.
Plompen EPC, Valk PJM, Chu I et al. Somatic Calreticulin Mutations in Patients with Budd-Chiari Syndrome and Portal Vein Thrombosis. Haematologica. 2015;32:226–228.
Marzac C, Plessier A, Kiladjian J-J et al. O079 : Calr somatic mutations in a prospective cohort of 308 patients with splanchnic vein thrombosis. Journal of Hepatology. 2015;62:S230.
Marjorie Roques, Ji-Hye Park, Anne Minello JN et al. Detection of the CALR mutation in the diagnosis of splanchnic vein thrombosis. British Journal of Haematology. 2015;169:595–604.
Haslam K, Langabeer SE. Incidence ofnCALR mutations in patients with splanchnic vein thrombosis. British Journal of Haematology. 2015;168(3):459–460.
Li M, De Stefano V, Song T et al. Prevalence of CALR mutations in splanchnic vein thrombosis: A systematic review and meta-analysis. Thrombosis Research. 2018;167:96–103.
Jadli A, Kulkarni B, Ghosh K et al. Non conventional mutations associated with myeloproliferative disorders are absent in splanchnic venous thrombosis cases. undefined. 2012;32(10):1596–1597.
Ho WK, Hong FS. CALR exon 9 mutations in idiopathic splanchnic vein thrombosis in an Australian cohort. Thrombosis Research. 2017;150:51–52.
Sekhar M, Patch D, Austen B et al. Calreticulin mutations and their importance in splanchnic vein thrombosis. Br J Haematol. 2016 Jul;174(1):158-60.
Mroczkowska-Bękarciak A, Wróbel T. BCR::ABL1-negative myeloproliferative neoplasms in the era of next-generation sequencing. Front Genet. 2023;14:1241912.
Wu S, Luo P, Yu Y et al. Next-generation sequencing redefines the diagnosis of triple-negative myeloproliferative neoplasms. Ann Hematol. 2022;101(3):705–708.
Qi X, Zhang C, Han G et al. Prevalence of the JAK2V617F mutation in Chinese patients with Budd-Chiari syndrome and portal vein thrombosis: A prospective study. Journal of Gastroenterology and Hepatology (Australia). 2012;27(6):1036–1043.
Qi X, Yang Z, Bai M et al. Meta-analysis : the significance of screening for JAK2V617F mutation in Budd – Chiari syndrome and portal venous system thrombosis. Alimentary Pharmacology & Therapeutics. 2011;33(10):1087–1103.
Qi X, Ren W, De Stefano V et al. Associations of Coagulation Factor V Leiden and Prothrombin G20210A Mutations With Budd-Chiari Syndrome and Portal Vein Thrombosis: A Systematic Review and Meta-analysis. Clinical Gastroenterology and Hepatology. 2014;12(11):1801–1812.
Hargreaves R, Subhan M, Alimam S et al. S199: a national retrospective cohort study of MPN-SVT: results from the uk myeloproliferative neoplasms associated splanchnic vein thrombosis (mascot) registry. HemaSphere. 2022;6:100–101.
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