Pathological and genomic features of myeloproliferative neoplasms associated with splanchnic vein thrombosis in a single-center cohort.
Myeloproliferative neoplasms
Next-generation sequencing
Outcome
Splanchnic vein thrombosis
Therapy
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
24
01
2023
accepted:
05
04
2023
medline:
15
5
2023
pubmed:
20
4
2023
entrez:
20
04
2023
Statut:
ppublish
Résumé
Here, we reviewed clinical-morphological data and investigated mutational profiles by NGS in a single-center series of 58 consecutive MPN-SVT patients admitted to our hospital between January 1979 and November 2021. We identified 15.5% of PV, 13.8% of ET, 34.5% of PMF, 8.6% of SMF and 27.6% of MPN-U. Most cases (84.5%) carried JAK2V617F mutation, while seven patients were characterized by other molecular markers, namely MPL in four and CALR mutations in three cases. NGS was performed in 54 (93.1%) cases: the most frequent additional mutations were found in TET2 (27.8%) and DNMT3A (16.7%) genes, whereas 25 (46.3%) patients had no additional mutation. Cases with JAK2V617F homozygosity had a higher median number of additional mutations than those with low allele burden. More importantly, all cases of leukemic evolution were characterized by a higher median number of co-mutations, and a co-mutational pattern of high-risk lesions, such as truncating mutations of ASXL1, bi-allelic TP53 loss, and CSMD1 mutations. Nevertheless, no difference was found between cases with and without additional somatic mutations regarding fibrotic progression, SVT recurrence, other thrombo-hemorrhagic complications, or death. After a median follow-up of 7.1 years, ten deaths were recorded; fibrotic progression/leukemic evolution was ascertained in one (1.7%) and six (10.3%) patients, respectively, while 22 (37.9%) patients suffered from recurrent thrombosis. In conclusion, our data underline the importance of using NGS analysis in the management of MPN-related SVT as it can support the MPN diagnosis, particularly in "triple-negative" cases, and provide additional information with potential consequences on prognosis and therapeutic strategies.
Identifiants
pubmed: 37079068
doi: 10.1007/s00277-023-05217-2
pii: 10.1007/s00277-023-05217-2
doi:
Substances chimiques
Janus Kinase 2
EC 2.7.10.2
Calreticulin
0
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1409-1420Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Barbui T, Carobbio A, Cervantes F et al (2010) Thrombosis in primary myelofibrosis: incidence and risk factors. Blood 115:778–782
pubmed: 19965680
doi: 10.1182/blood-2009-08-238956
Falanga A, Marchetti M (2012) Thrombotic disease in the myeloproliferative neoplasms. Hematology (Am Soc Hematol Educ Program) 2012:571–581
pubmed: 23233637
doi: 10.1182/asheducation.V2012.1.571.3798557
Harrison CN, Campbell PJ, Buck G et al (2005) Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 353:33–45
pubmed: 16000354
doi: 10.1056/NEJMoa043800
Gisslinger H, Gotic M, Holowiecki J et al (2013) Anagrelide compared to hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood 121:1720–1728
pubmed: 23315161
pmcid: 3591796
doi: 10.1182/blood-2012-07-443770
Carobbio A, Thiele J, Passamonti F et al (2011) Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood 117:5857–5859
pubmed: 21490340
doi: 10.1182/blood-2011-02-339002
Marchioli R, Finazzi G, Landolfi R et al (2005) Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol 23:2224–2232
pubmed: 15710945
doi: 10.1200/JCO.2005.07.062
Dentali F, Ageno W, Rumi E et al (2014) Cerebral venous thrombosis and myeloproliferative neoplasms: results from two large databases. Thromb Res 134:41–43
pubmed: 24787989
doi: 10.1016/j.thromres.2014.03.040
Martinelli I, De Stefano V, Carobbio A et al (2014) Cerebral vein thrombosis in patients with Philadelphia-negative myeloproliferative neoplasms. An European Leukemia Net study. Am J Hematol 89:E200–E205
pubmed: 25042466
doi: 10.1002/ajh.23809
Thatipelli MR, McBane RD, Hodge DO, Wysokinski WE (2010) Survival and recurrence in patients with splanchnic vein thrombosis. Clin Gastroenterol Hepatol 8:200–205
pubmed: 19782767
doi: 10.1016/j.cgh.2009.09.019
Finazzi G, De Stefano V, Barbui T (2013) Are MPNs Vascular Diseases? Curr Hematol Malig Rep 8:307–316
pubmed: 24037420
doi: 10.1007/s11899-013-0176-z
Cortelezzi A, Moia M, Falanga A et al (2005) Incidence of thrombotic complications in patients with haematological malignancies with central venous catheters: a prospective multicentre study. Br J Haematol 129:811–817
pubmed: 15953009
doi: 10.1111/j.1365-2141.2005.05529.x
Elkrief L, Payancé A, Plessier A et al (2023) Management of splanchnic vein thrombosis. JHEP Rep. https://doi.org/10.1016/j.jhepr.2022.100667
doi: 10.1016/j.jhepr.2022.100667
pubmed: 36941824
pmcid: 10023986
Smalberg JH, Arends LR, Valla DC, Kiladjian JJ, Janssen HL, Leebeek FW (2012) Myeloproliferative neoplasms in Budd-Chiari syndrome and portal vein thrombosis: a meta-analysis. Blood 120:4921–4928
pubmed: 23043069
doi: 10.1182/blood-2011-09-376517
Darwish Murad S, Plessier A, Hernandez-Guerra M et al (2009) Etiology, management, and outcome of the Budd-Chiari syndrome. Ann Intern Med 151:167–175
pubmed: 19652186
doi: 10.7326/0003-4819-151-3-200908040-00004
Bayraktar Y, Harmanci O, Buyukasik Y et al (2008) JAK2V617F mutation in patients with portal vein thrombosis. Dig Dis Sci 53:2778–2783
pubmed: 18343999
doi: 10.1007/s10620-008-0225-y
Valla D, Casadevall N, Huisse MG et al (1988) Etiology of portal vein thrombosis in adults: a prospective evaluation of primary myeloproliferative disorders. Gastroenterology 94:1063–1069
pubmed: 3345875
doi: 10.1016/0016-5085(88)90567-7
Donadini MP, Dentali F, Ageno W (2012) Splanchnic vein thrombosis: new risk factors and management. Thromb Res 129:S93–S96
pubmed: 22682143
doi: 10.1016/S0049-3848(12)70025-7
Chagneau-Derrode C (2013) Impact of cytoreductive therapy on the outcome of patients with myeloproliferative neoplasms and hepato-splanchnic vein thrombosis. Hepatology 58:847A-898A
Primignani M, Barosi G, Bergamaschi G et al (2006) Role of the JAK2 mutation in the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis. Hepatology 44:1528–1534
pubmed: 17133457
doi: 10.1002/hep.21435
Jones C, Levy Y, Tong AW (2014) Elevated serum erythropoietin in a patient with polycythaemia vera presenting with Budd-Chiari syndrome. BMJ Case Rep 2014:1–4
doi: 10.1136/bcr-2014-205663
Sekhar M, McVinnie K, Burroughs AK (2013) Splanchnic vein thrombosis in myeloproliferative neoplasms. Br J Haematol 162:730–747
pubmed: 23855810
doi: 10.1111/bjh.12461
Bergamaschi GM, Primignani M, Barosi G et al (2008) MPL and JAK2 exon 12 mutations in patients with the Budd-Chiari syndrome or extrahepatic portal vein obstruction. Blood 111:4418
pubmed: 18398061
doi: 10.1182/blood-2008-02-137687
Kiladjian JJ, Cervantes F, Leebeek FW et al (2008) The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood 111:4922–4929
pubmed: 18250227
doi: 10.1182/blood-2007-11-125328
Fiorini A, Chiusolo P, Rossi E et al (2009) Absence of the JAK2 exon 12 mutations in patients with splanchnic venous thrombosis and without overt myeloproliferative neoplasms. Am J Hematol 84:126–127
pubmed: 19105231
doi: 10.1002/ajh.21335
Magaz M, Alvarez-Larrán A, Colomer D et al (2021) Next-generation sequencing in the diagnosis of non-cirrhotic splanchnic vein thrombosis. J Hepatol 74:89–95
pubmed: 32679300
doi: 10.1016/j.jhep.2020.06.045
Iurlo A, Cattaneo D, Gianelli U, Fermo E, Augello C, Cortelezzi A (2015) Molecular analyses in the diagnosis of myeloproliferative neoplasm-related splanchnic vein thrombosis. Ann Hematol 94:881–882
pubmed: 25377046
doi: 10.1007/s00277-014-2249-z
Klampfl T, Gisslinger H, Harutyunyan AS et al (2013) Somatic mutations of calreticulin in myeloproliferative neoplasms. N Eng J Med 369:2379–2390
doi: 10.1056/NEJMoa1311347
Nangalia J, Massie CE, Baxter EJ et al (2013) Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Eng J Med 369:2391–2405
doi: 10.1056/NEJMoa1312542
Turon F, Cervantes F, Colomer D, Baiges A, Hernández-Gea V, Garcia-Pagán JC (2015) Role of calreticulin mutations in the etiological diagnosis of splanchnic vein thrombosis. J Hepatol 62:72–74
pubmed: 25173966
doi: 10.1016/j.jhep.2014.08.032
Haslam K, Langabeer SE (2015) Incidence of CALR mutations in patients with splanchnic vein thrombosis. Br J Haematol 168:459–460
pubmed: 25223992
doi: 10.1111/bjh.13121
Gianelli U, Iurlo A, Cattaneo D et al (2015) Discrepancies between bone marrow histopathology and clinical phenotype in BCR-ABL1-negative myeloproliferative neoplasms associated with splanchnic vein thrombosis. Leuk Res 39:525–529
pubmed: 25840747
doi: 10.1016/j.leukres.2015.03.009
Grinfeld J, Nangalia J, Baxter EJ et al (2018) Classification and personalized prognosis in myeloproliferative neoplasms. N Engl J Med 379:1416–1430
pubmed: 30304655
pmcid: 7030948
doi: 10.1056/NEJMoa1716614
Ortmann CA, Kent DG, Nangalia J et al (2015) Effect of mutation order on myeloproliferative neoplasms. N Engl J Med 372:601–612
pubmed: 25671252
pmcid: 4660033
doi: 10.1056/NEJMoa1412098
Lavu S, Szuber N, Mudireddy M et al (2018) Splanchnic vein thrombosis in patients with myeloproliferative neoplasms: the Mayo clinic experience with 84 consecutive cases. Am J Hematol 93:E61–E64
pubmed: 29194707
doi: 10.1002/ajh.24993
Cattaneo D, Gianelli U, Bianchi P, Cortelezzi A, Iurlo A (2018) Heterogeneity among splanchnic vein thrombosis associated with myeloproliferative neoplasms. Eur J Intern Med 52:e25–e26
pubmed: 29567096
doi: 10.1016/j.ejim.2018.03.009
Hoekstra J, Bresser EL, Smalberg JH, Spaander MC, Leebeek FW, Janssen HL (2011) Long-term follow-up of patients with portal vein thrombosis and myeloproliferative neoplasms. J Thromb Haemost 9:2208–2214
pubmed: 22040061
doi: 10.1111/j.1538-7836.2011.04484.x
Gangat N, Wolanskyj AP, Tefferi A (2006) Abdominal vein thrombosis in essential thrombocythemia: prevalence, clinical correlates, and prognostic implications. Eur J Haematol 77:327–333
pubmed: 16856928
doi: 10.1111/j.1600-0609.2006.00715.x
De Stefano V, Vannucchi AM, Ruggeri M et al (2016) Splanchnic vein thrombosis in myeloproliferative neoplasms: risk factors for recurrences in a cohort of 181 patients. Blood Cancer J 6:e493
pubmed: 27813534
pmcid: 5148051
doi: 10.1038/bcj.2016.103
Sant’Antonio E, Guglielmelli P, Pieri L et al (2020) Splanchnic vein thromboses associated with myeloproliferative neoplasms: An international, retrospective study on 518 cases. Am J Hematol 95:156–166
pubmed: 31721282
doi: 10.1002/ajh.25677
Barosi G, Vannucchi AM, De Stefano V et al (2014) Identifying and addressing unmet clinical needs in Ph-neg classical myeloproliferative neoplasms: a consensus-based SIE, SIES, GITMO position paper. Leuk Res 38:155–160
pubmed: 24378116
doi: 10.1016/j.leukres.2013.09.008
Marchioli R, Finazzi G, Specchia G et al (2013) Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med 368:22–33
pubmed: 23216616
doi: 10.1056/NEJMoa1208500
Barosi G, Mesa RA, Thiele J et al (2008) Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia 22:437–438
pubmed: 17728787
doi: 10.1038/sj.leu.2404914
Swerdlow SH, Campo E, Harris L et al. (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th ed. IARC, Lyon, 127–129
Baxter EJ, Scott LM, Campbell PJ et al (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365:1054–1061
pubmed: 15781101
doi: 10.1016/S0140-6736(05)71142-9
Bolli N, Manes N, McKerrell T et al (2015) Characterization of gene mutations and copy number changes in acute myeloid leukemia using a rapid target enrichment protocol. Haematologica 100:214–222
pubmed: 25381129
pmcid: 4803131
doi: 10.3324/haematol.2014.113381
McKerrell T, Moreno T, Ponstingl H et al (2016) Development and validation of a comprehensive genomic diagnostic tool for myeloid malignancies. Blood 128:e1–e9
pubmed: 27121471
pmcid: 4937362
doi: 10.1182/blood-2015-11-683334
Nik-Zainal S, Van Loo P, Wedge DC et al (2012) The life history of 21 breast cancers. Cell 149:994–1007
pubmed: 22608083
pmcid: 3428864
doi: 10.1016/j.cell.2012.04.023
Bolli N, Biancon G, Moarii M et al (2018) Analysis of the genomic landscape of multiple myeloma highlights novel prognostic markers and disease subgroups. Leukemia 32:2604–2616
pubmed: 29789651
pmcid: 6092251
doi: 10.1038/s41375-018-0037-9
Ziccheddu B, Biancon G, Bagnoli F et al (2020) Integrative analysis of the genomic and transcriptomic landscape of double-refractory multiple myeloma. Blood Adv 4:830–844
pubmed: 32126144
pmcid: 7065476
doi: 10.1182/bloodadvances.2019000779
Rack KA, van den Berg E, Haferlach C et al (2019) European recommendations and quality assurance for cytogenomic analysis of haematological neoplasms. Leukemia 33:1851–1867
pubmed: 30696948
pmcid: 6756035
doi: 10.1038/s41375-019-0378-z
Gianelli U, Iurlo A, Vener C et al (2008) The significance of bone marrow biopsy and JAK2V617F mutation in the differential diagnosis between the early pre-polycythemic phase of polycythemia vera and essential thrombocythemia. Am J Clin Pathol 130:336–342
pubmed: 18701405
doi: 10.1309/6BQ5K8LHVYAKUAF4
Spivak JL, Silver RT (2011) The treatment of essential thrombocytosis revisited. Blood 28:1179–1180
doi: 10.1182/blood-2011-03-341925
Silver RT, Chow W, Orazi A, Arles SP, Goldsmith SJ (2013) Evaluation of WHO criteria for diagnosis of polycythemia vera: a prospective analysis. Blood 122:1881–1886
pubmed: 23900239
doi: 10.1182/blood-2013-06-508416
Rosti V, Villani L, Riboni R et al (2013) Spleen endothelial cells from patients with myelofibrosis harbor the JAK2V617F mutation. Blood 121:360–368
pubmed: 23129323
doi: 10.1182/blood-2012-01-404889
Giordano G, Napolitano M, Cellurale M et al (2022) Circulating Endothelial Cell Levels Correlate with Treatment Outcomes of Splanchnic Vein Thrombosis in Patients with Chronic Myeloproliferative Neoplasms. J Pers Med 12:364
pubmed: 35330364
pmcid: 8954048
doi: 10.3390/jpm12030364
Pieri L, Paoli C, Arena U et al (2017) Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms. Am J Hematol 92:187–195
pubmed: 27880982
doi: 10.1002/ajh.24614
Barosi G, Buratti A, Costa A et al (1991) An atypical myeloproliferative disorder with high thrombotic risk and slow disease progression. Cancer 68:2310–2318
pubmed: 1913467
doi: 10.1002/1097-0142(19911115)68:10<2310::AID-CNCR2820681034>3.0.CO;2-2
Segura-Díaz A, Stuckey R, Florido Y et al (2020) Thrombotic risk detection in patients with polycythemia vera: the predictive role of DNMT3A/TET2/ASXL1 mutations. Cancers (Basel) 12:934
pubmed: 32290079
doi: 10.3390/cancers12040934
Solary E, Bernard OA, Tefferi A, Fuks F, Vainchenker W (2014) The Ten-Eleven Translocation-2 (TET2) gene in hematopoiesis and hematopoietic diseases. Leukemia 28:485–496
pubmed: 24220273
doi: 10.1038/leu.2013.337
Delhommeau F, Dupont S, Della Valle V et al (2009) Mutation in TET2 in myeloid cancers. N Engl J Med 360:2289–2301
pubmed: 19474426
doi: 10.1056/NEJMoa0810069
Colaizzo D, Tiscia GL, Pisanelli D et al (2010) New TET2 gene mutations in patients with myeloproliferative neoplasms and splanchnic vein thrombosis. J Thromb Haemost 8:1142–1144
pubmed: 20156304
doi: 10.1111/j.1538-7836.2010.03810.x
Sousos N, Ní Leathlobhair M, Simoglou Karali C et al (2022) In utero origin of myelofibrosis presenting in adult monozygotic twins. Nat Med 28:1207–1211
pubmed: 35637336
pmcid: 9205768
doi: 10.1038/s41591-022-01793-4
Fuster JJ, MacLauchlan S, Zuriaga MA et al (2017) Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science 355:842–847
pubmed: 28104796
pmcid: 5542057
doi: 10.1126/science.aag1381
Laurie CC, Laurie CA, Rice K et al (2012) Detectable clonal mosaicism from birth to old age and its relationship to cancer. Nat Genet 44:642–650
pubmed: 22561516
pmcid: 3366033
doi: 10.1038/ng.2271
Jaiswal S, Fontanillas P, Flannick J et al (2014) Age-related clonal hematopoiesis associated with adverse outcomes. N Engl J Med 371:2488–2498
pubmed: 25426837
pmcid: 4306669
doi: 10.1056/NEJMoa1408617
Genovese G, Kähler AK, Handsaker RE et al (2014) Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med 371:2477–2487
pubmed: 25426838
pmcid: 4290021
doi: 10.1056/NEJMoa1409405
Steensma DP, Bejar R, Jaiswal S et al (2015) Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood 126:9–16
pubmed: 25931582
pmcid: 4624443
doi: 10.1182/blood-2015-03-631747
Jaiswal S, Natarajan P, Silver AJ et al (2017) Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med 377:111–121
pubmed: 28636844
pmcid: 6717509
doi: 10.1056/NEJMoa1701719
Westbrook R, Lea N, Mohamedali A et al (2012) Prevalence and clinical outcomes of the 46/1 haplotype, Janus kinase 2 mutations, and ten-eleven translocation 2 mutations in Budd-Chiari syndrome and their impact on thrombotic complications post liver transplantation. Liver Transpl 18:819–827
pubmed: 22467227
doi: 10.1002/lt.23443
How J, Zhou A, Oh ST (2017) Splanchnic vein thrombosis in myeloproliferative neoplasms: pathophysiology and molecular mechanisms of disease. Ther Adv Hematol 8:107–118
pubmed: 28246554
doi: 10.1177/2040620716680333
Iurlo A, Cattaneo D, Gianelli U (2019) Blast Transformation in Myeloproliferative Neoplasms: Risk Factors, Biological Findings, and Targeted Therapeutic Options. Int J Mol Sci 20:1839
pubmed: 31013941
pmcid: 6514804
doi: 10.3390/ijms20081839
Debureaux PE, Cassinat B, Soret-Dulphy J et al (2020) Molecular profiling and risk classification of patients with myeloproliferative neoplasms and splanchnic vein thromboses. Blood Adv 4:3708–3715
pubmed: 32777065
pmcid: 7422133
doi: 10.1182/bloodadvances.2020002414
Cattaneo D, Croci GA, Bucelli C et al (2021) Triple-Negative Essential Thrombocythemia: Clinical-Pathological and Molecular Features. A Single-Center Cohort Study. Front Oncol 11:637116
pubmed: 33791220
pmcid: 8006378
doi: 10.3389/fonc.2021.637116
Maddali M, Venkatraman A, Kulkarni UP et al (2022) Molecular characterization of triple-negative myeloproliferative neoplasms by next-generation sequencing. Ann Hematol 101:1987–2000
pubmed: 35840818
doi: 10.1007/s00277-022-04920-w