Frequency of mutations in the JAK2, MPL, and CALR genes in BCR::ABL1-negative chronic myeloproliferative neoplasms in patients from two hospitals in the city of Medellín, Colombia, during 2020-2021
DOI:
https://doi.org/10.35509/01239015.861Keywords:
myeloproliferative disorders, BCR-ABL1, JAK2, MPL, CALRAbstract
Background: In the 2016 WHO classification, the subgroup of BCR::ABL1 negative chronic myeloproliferative neoplasms (MPNs) is made up of three entities: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), which are characterized by mutations in the JAK2, MPL, and CALR genes with important diagnostic and prognostic value.
Objective: To determine the frequency of mutations in the JAK2, MPL, and CALR genes in BCR::ABL1 negative chronic MPNs and to explore the association between the type of BCR::ABL1 negative chronic MPNs, mutational status, and blood count parameters in patients from two hospitals in the city of Medellín, Colombia, during 2020-2021.
Methods: Cross-sectional descriptive observational study, which included patients with a diagnosis of BCR::ABL1-negative MPNs. JAK2, MPL, and CALR genes were assessed by massive sequencing using the illumina® TruSight One panel. A descriptive analysis was performed by estimating relative and absolute frequencies or summary measures (central tendency, dispersion, or position) depending on the nature of the variables.
Results: A total of 24 patients were included in the study; 37.5% of the cases corresponded to patients with ET. The distribution according to mutational status was non-mutated or triple negative in 13 cases (54.2%) and mutated in 11 cases (45.8%). The pathogenic mutations found in order of frequency were JAK2 (82%), MPL (9%), and CALR (9%).
Conclusion: Our study is consistent with what has been reported in the world literature, with JAK2 V617F being the most frequent mutation in BCR::ABL1-negative MPNs. Lower frequencies for CALR and MPL may be influenced by the sample size.
Author Biographies
Erika Pino, Grupo Hematopatología Molecular, Universidad de Antioquia, Medellín, Colombia.
1. Grupo Hematopatología Molecular, Universidad de Antioquia, Medellín, Colombia.
Paola Acevedo, Grupo Hematopatología Molecular, Universidad de Antioquia, Medellín, Colombia.
1. Grupo Hematopatología Molecular, Universidad de Antioquia, Medellín, Colombia.
Kenny Gálvez, Servicio de Hematología y Trasplante de Médula Ósea, Hospital Pablo Tobón Uribe, Medellín, Colombia.
2. Servicio de Hematología y Trasplante de Médula Ósea, Hospital Pablo Tobón Uribe, Medellín, Colombia.
Beatriz Aristizábal, Laboratorio Unidad de Investigación Genética Molecular (UNIGEM), Medellín, Colombia.
3. Laboratorio Unidad de Investigación Genética Molecular (UNIGEM), Medellín, Colombia.
References
Jiménez SI. Neoplasias mieloproliferativas: De la clínica a la biología molecular. Acta Médica Colomb. 2017;42(1):15–7. Disponible en: https://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S0120-24482017000100015
Labastida-Mercado N, Galindo-Becerra S, Garcés-Eisele J, Colunga-Pedraza P, Guzman-Olvera V, Reyes-Nuñez V, et al. The mutation profile of JAK2, MPL and CALR in Mexican patients with Philadelphia chromosome-negative myeloproliferative neoplasms. Hematol Oncol Stem Cell Ther. 2015;8(1):16–21. https://doi.org/10.1016/j.hemonc.2014.12.002
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Leri SAP, Stein H, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4 edición. 2017. 586 p. Available from: https://publications.iarc.fr/Book-And-Report-Series/Who-Classification-Of-Tumours/WHO-Classification-Of-Tumours-Of-Haematopoietic-And-Lymphoid-Tissues-2017
Videla YP, Quintana S, Pérez Maturo J, Di Gerónimo V, Martín N, Pagani F. Mutaciones en JAK2, MPL y CALR en neoplasias mieloproliferativas: análisis de disociación de alta resolución. Acta Bioquímica Clínica Latinoam. 2017;51(4):629–36. Disponible en: https://www.redalyc.org/articulo.oa?id=53554497009
Srour SA, Devesa SS, Morton LM, Check DP, Curtis RE, Linet MS, et al. Incidence and patient survival of myeloproliferative neoplasms and myelodysplastic/myeloproliferative neoplasms in the United States, 2001-2012. Br J Haematol. 2016;174(3):382–96. https://doi.org/10.1111/bjh.14061
Solano JC, Casas CP, Abello V, Solano MH. Características clínicas y paraclínicas de las neoplasias mielproliferativas crónicas cromosoma filadelfia negativas. Acta Médica Colomb. 2012;37(2):66–73. Disponible en: https://www.redalyc.org/articulo.oa?id=163124275004
Mehta J, Wang H, Iqbal SU, Mesa R. Epidemiology of myeloproliferative neoplasms in the United States. Leuk Lymphoma. 2014;55(3):595–600. https://doi.org/10.3109/10428194.2013.813500
Titmarsh GJ, Duncombe AS, Mcmullin MF, O’Rorke M, Mesa R, De Vocht F, et al. How common are myeloproliferative neoplasms? A systematic review and meta-analysis. Am J Hematol. 2014;89(6):581–7. https://doi.org/10.1002/ajh.23690
Instituto Nacional de Cancerología (INC). Anuario estadístico 2019. Bogotá, D. C.: INC; 2021. Disponible en: https://www.cancer.gov.co/conozca-sobre-cancer-1/publicaciones/anuario-estadistico-2019
Wu Z, Zhang X, Xu X, Chen Y, Hu T, Kang Z, et al. The mutation profile of JAK2 and CALR in Chinese Han patients with Philadelphia chromosome-negative myeloproliferative neoplasms. J Hematol Oncol. 2014;7(1):1–10. https://doi.org/10.1186/s13045-014-0048-6
Abello V, Quintero G, Espinosa D, Solano MH, Casas CP, Saavedra D, et al. Descripción de las características clínicas de las neoplasias mieloproliferativas crónicas (NMPC). Primer informe del registro colombiano de NMPC. Acta Médica Colomb. 2017;42(1):35–41. Available from: https://pesquisa.bvsalud.org/portal/resource/pt/biblio-886337
León-Basantes G, Abello-Polo V, Casas-Patarroyo CP, Espinosa-Redondo D, Solano-Trujillo MH. Calidad de vida en pacientes con neoplasias mieloproliferativas crónicas Filadelfia negativas. Acta Medica Colomb. 2019;44(2):82–90. Disponible en: https://www.redalyc.org/articulo.oa?id=163162170005
Sieza Y, Camilo I Di, Mazziotta L, Archuby ML, Riva ME, Orellano L. Distribución de mutaciones en JAK2, MPL y CALR en pacientes con sospecha de neoplasias mieloproliferativas crónicas Phi negativas provenientes de hospitales públicos de la provincia de Buenos Aires. Rev Hematol. 2018;22(2):151–6. Disponible en: https://revistahematologia.com.ar/index.php/Revista/article/view/20
Song J, Hussaini M, Zhang H, Shao H, Qin D, Zhang X, et al. Comparison of the mutational profiles of primary myelofibrosis, polycythemia vera, and essential thrombocytosis. Am J Clin Pathol. 2017;147(5):444–52. https://doi.org/10.1093/ajcp/aqw222.
Jaradat SA, Khasawneh R, Kamal N, Matalka I, Al-Bishtawi M, Al-Sweedan S, et al. Analysis of JAK2V617F mutation in Jordanian patients with myeloproliferative neoplasms. Hematol Oncol Stem Cell Ther. 2015;8(4):160–6. https://doi.org/10.1016/j.hemonc.2015.07.004
Lundberg P, Karow A, Nienhold R, Looser R, Hao-Shen H, Nissen I, et al. Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. Blood. 2014;123(14):2220–8. https://doi.org/10.1182/blood-2013-11-537167
Soliman EA, El-Ghlban S, El-Aziz SA, Abdelaleem A, Shamaa S, Abdel-Ghaffar H. JAK2, CALR, and MPL mutations in egyptian patients with classic Philadelphia-negative myeloproliferative neoplasms. Clin Lymphoma, Myeloma Leuk. 2020;20(10):e645–51. https://doi.org/10.1016/j.clml.2020.05.011
Benmoussa A, Dehbi H, Fehri S, Quessar A, Nadifi S. JAK2-V617F mutation in Moroccan patients with myeloproliferative disorders: Contribution, diagnosis and therapeutic prospects. Pathol Biol. 2011;59(4):2009–12. https://doi.org/10.1016/j.patbio.2009.06.005
Ojeda MJ, Bragós IM, Calvo KL, Williams GM, Carbonell MM, Pratti AF. CALR, JAK2 and MPL mutation status in Argentinean patients with BCR-ABL1- negative myeloproliferative neoplasms. Hematology. 2018;23(4):208–11. https://doi.org/10.1080/10245332.2017.1385891
Vainchenker W, Kralovics R. Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood. 2017;129(6):667–79. https://doi.org/10.1182/blood-2016-10-695940
Vannucchi AM, Antonioli E, Guglielmelli P, Rambaldi A, Barosi G, Marchioli R, et al. Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia. Blood. 2007;110(3):840–6. https://doi.org/10.1182/blood-2006-12-064287
Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3(7):1140–51. https://doi.org/10.1371/journal.pmed.0030270
Speletas M, Katodritou E, Daiou C, Mandalab E, Papadakis E, Kioumi A, et al. Correlations of JAK2–V617F mutation with clinical and laboratory findings in patients with myeloproliferative disorders. Leuk Res. 2007;31(10):1053–1062. https://doi.org/10.1016/j.leukres.2006.09.005
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