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Among the chronic myeloproliferative neoplasms (MPNs) not associated with BCR-ABL mutations are polycythemia vera, primary myelofibrosis, and essential thrombocythemia. These diseases are caused by gene mutations, such as the JAK2, MPL, and CALR genes, which regulate the JAK-STAT signaling pathway.

This study aimed to establish the frequencies of mutations in the JAK2, MPL, and CALR genes in Colombian patients with a negative clinical diagnosis of BCR-ABL chronic myeloproliferative neoplasms.

The JAK2 V617F and MPL W515K mutations and deletions or insertions in exon 9 of the CALR gene were analyzed in 52 Colombian patients with polycythemia vera, primary myelofibrosis, and essential thrombocythemia.

The JAK2V617F mutation was carried by 51.9% of the patients, the CALR mutation by 23%, and the MPL mutation by 3.8%; 23% were triple-negative for the mutations analyzed. Six mutation types in CALR were identified in these neoplasms, one of which has not been previously reported. Additionally, one patient presented a double mutation in the CALR and JAK2 genes. Regarding the hematological results for the mutations, significant differences were found in the hemoglobin level, hematocrit level, and platelet count among the three neoplasms.

Thus, this study demonstrates the importance of the molecular characterization of the JAK2, CALR and MPL mutations in Colombian patients (the genetic context of which remains unclear in the abovementioned neoplasms) to achieve an accurate diagnosis, a good prognosis, adequate management, and patient survival.

Ana Isabel Giraldo-Rincon, 1 Universidad de Antioquia, Facultad de Medicina, Unidad de Genética Médica, Medellín, Colombia


Sara Naranjo Molina, Universidad de Antioquia, Facultad de Medicina, Unidad de Genética Médica, Medellín, Colombia.


Natalia Gomez-Lopera, Universidad de Antioquia, Facultad de Medicina, Unidad de Genética Médica, Medellín, Colombia.


Daniel Aguirre Acevedo, Universidad de Antioquia, Grupo Académico de Epidemiología Clinica, Medellin, Colombia.


Andrea Ucroz Benavidez, Universidad de Antioquia, Facultad de Medicina, Unidad de Genética Médica, Medellín, Colombia.


Kenny Gálvez Cárdenas, Hospital Pablo Tobón Uribe, Medellín, Colombia


Francisco Cuellar Ambrosí, Hospital Alma Mater, Medellín, Colombia


Jose Domingo Torres, Hospital Universitario San Vicente Fundación, Medellín, Colombia.


Sigifredo Ospina, Hospital Universitario San Vicente Fundación, Medellín, Colombia.


Katherine Palacio, Universidad de Antioquia, Facultad de Medicina, Unidad de Genética Médica, Medellín, Colombia


Lina Gaviria Jaramillo, Hospital Universitario San Vicente Fundación, Medellín, Colombia


Carlos Mario Muñeton, Universidad de Antioquia, Facultad de Medicina, Unidad de Genética Médica, Medellín, Colombia


Gonzalo Vasquez Palacio, 1 Universidad de Antioquia, Facultad de Medicina, Unidad de Genética Médica, Medellín, Colombia


Giraldo-Rincon, A. I., Naranjo Molina, S., Gomez-Lopera, N., Aguirre Acevedo, D., Ucroz Benavidez, A., Gálvez Cárdenas, K., Cuellar Ambrosí, F., Torres, J. D., Ospina, S., Palacio, K., Gaviria Jaramillo, L., Muñeton, C. M., & Vasquez Palacio, G. (2023). JAK2, CALR, and MPL Mutation Profiles in Colombian patients with BCR-ABL Negative Myeloproliferative Neoplasms. Colombia Medica, 54(3), e2035353. (Original work published September 30, 2023)

Nann D, Fend F. Synoptic diagnostics of myeloproliferative neoplasms: Morphology and molecular genetics. Cancers. 2021;13(14):1-22. PMid:34298741 PMCid:PMC8303289

Shallis RM, Zeidan AM, Wang R, Podoltsev NA. Epidemiology of the Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms. Hematology/Oncology Clinics of North America. 2021;35(2):177-89. PMid:33641862

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 ) Description of the clinical characteristics of chronic myeloproliferative neoplasms ( MPNs ) First report of the colombian registry of MPNs. Acta Médica Colombiana. 2017;42(1):35-41.

Langabeer SE, Andrikovics H, Asp J, Bellosillo B, Carillo S, Haslam K, et al. Molecular diagnostics of myeloproliferative neoplasms. European J Haematol. 2015;95(4):270-9. PMid:25951317

Ferreira Cristina S, Polo B, Lacerda JF. Somatic Mutations in Philadelphia Chromosome-Negative Myeloproliferative Neoplasms. Seminars in Hematology. 2018;55(4):215-22. PMid:30502850

Araki M, Komatsu N. The role of calreticulin mutations in myeloproliferative neoplasms. International Journal of Hematology. 2020;111(2):200-5. PMid:31848992

Vainchenker W, Dusa A, Constantinescu SN. JAKs in pathology: Role of Janus kinases in hematopoietic malignancies and immunodeficiencies. Seminars in Cell and Developmental Biology. 2008;19(4):385-93. PMid:18682296

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. American Journal of Clinical Pathology. 2017;147(5):444-52. PMid:28419183 PMCid:PMC5402718

Tefferi A, Pardanani A. Myeloproliferative neoplasms: A contemporary review. JAMA Oncology. 2015;1(1):97-105. PMid:26182311

Brown NA, Elenitoba-Johnson KSJ. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Hematolymphoid Tumours. Head and Neck Pathology. 2017;11(1):96-109. PMid:28247223 PMCid:PMC5340738

Furtado LV, Weigelin HC, Elenitoba-Johnson KSJ, Betz BL. A Multiplexed fragment analysis-based assay for detection of JAK2 exon 12 mutations. Journal of Molecular Diagnostics. 2013;15(5):592-9. PMid:23810504

Jones AV, Ward D, Lyon M, Leung W, Callaway A, Chase A, et al. Evaluation of methods to detect CALR mutations in myeloproliferative neoplasms. Leukemia Research. 2015;39(1):82-7. PMid:25499808

Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic Mutations of Calreticulin in Myeloproliferative Neoplasms. New England Journal of Medicine. 2013;369(25):2379-90. PMid:24325356

R Core Team (2017). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria.

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. PMid:28990497

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. Hematology/ Oncology and Stem Cell Therapy. 2015;8(1):16-21. PMid:25637689

Kim SY, Im K, Park SN, Kwon J, Kim JA, Lee DS. CALR, JAK2, and MPL mutation profiles in patients with four different subtypes of myeloproliferative neoplasms: Primary myelofibrosis, essential thrombocythemia, polycythemia vera, and myeloproliferative neoplasm, unclassifiable. American Journal of Clinical Pathology. 2015;143(5):635-44. PMid:33936230 PMCid:PMC8085288

Szuber N, Mudireddy M, Nicolosi M, Penna D, Vallapureddy R, Lasho TL, et al. 3,023 Mayo Clinic Patients with Myeloproliferative Neoplasms: Risk-Stratified Comparison of Survival and Outcomes Data Among Disease Subgroups. Blood. 2018;132(Supplement 1):3035-3035. PMid:30824279

Misawa K, Yasuda H, Araki M, Ochiai T, Morishita S, Shirane S, et al. Mutational subtypes of JAK2 and CALR correlate with different clinical features in Japanese patients with myeloproliferative neoplasms. International Journal of Hematology. 2018;107(6):673-80. PMid:29464483

Pietra D, Rumi E, Ferretti V V., Di Buduo CA, Milanesi C, Cavalloni C, et al. Differential clinical effects of different mutation subtypes in CALR-mutant myeloproliferative neoplasms. Leukemia. 2016;30(2):431-8. DOI: 10.1038/leu.2015.277 PMid:26449662 PMCid:PMC4740452

Machado-Neto JA, de Melo Campos P, de Albuquerque DM, Costa FF, Lorand-Metze I, Olalla Saad ST, et al. Somatic mutations of calreticulin in a Brazilian cohort of patients with myeloproliferative neoplasms. Revista Brasileira de Hematologia e Hemoterapia. 2015;37(3):211-4. PMid:26041426 PMCid:PMC4459485

Singdong R, Siriboonpiputtana T, Chareonsirisuthigul T, Kongruang A, Limsuwanachot N, Sirirat T, et al. Characterization and Prognosis Significance of JAK2 (V617F), MPL, and CALR Mutations in PhiladelphiaNegative Myeloproliferative Neoplasms. Asian Pacific Journal of Cancer Prevention. 2016;17(10):4647-53.

Lang T, Nie Y, Wang Z, Huang Q, An L, Wang Y, et al. Correlation analysis between JAK2, MPL, and CALR mutations in patients with myeloproliferative neoplasms of Chinese Uygur and Han nationality and their clinical characteristics. Journal of International Medical Research. 2018;46(11):4650-9. PMid:30084272 PMCid:PMC6259388

Rabade N, Subramanian PG, Kodgule R, Raval G, Joshi S, Chaudhary S, et al. Molecular genetics of BCR-ABL1 negative myeloproliferative neoplasms in India. Indian Journal of Pathology and Microbiology. 2018;61(2):209-13. PMid:29676359

Nunes DPT, de Lima LT, Chauffaille M de L, Mitne-Neto M, dos Santos MT, Cliquet MG, et al. CALR mutations screening in wild type JAK2V617F and MPLW515K/L Brazilian myeloproliferative neoplasm patients. Blood Cells, Molecules, and Diseases. 2015;55(3):236-40. PMid:26227853

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. Clinical Lymphoma, Myeloma and Leukemia. 2020;20(10):e645-51. PMid:32591258

Vainchenker W, Kralovics R. Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood. 2017;129(6):667-79. PMid:28028029

Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: A study of 1182 patients. Blood. 2006;108(10):3472-6. PMid:16868251

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. PMid:24478400

Mcgaffin G, Harper K, Stirling D, Mclintock L. JAK2 V617F and CALR mutations are not mutually exclusive; findings from retrospective analysis of a small patient cohort. British Journal of Haematology. 2014;167(2):276-8. PMid:24935260

Jeong JH, Lee HT, Seo JY, Seo YH, Kim KH, Kim MJ, et al. Screening PCR versus sanger sequencing:Detection of CALR mutations in patients with thrombocytosis. Annals of Laboratory Medicine. 2016;36(4):291-9. PMid:27139600 PMCid:PMC4855047

Chen CC, Gau JP, Chou HJ, You JY, Huang CE, Chen YY, et al. Frequencies, clinical characteristics, and outcome of somatic CALR mutations in JAK2-unmutated essential thrombocythemia. Annals of Hematology. 2014;93(12):2029-36. PMid:25015052

Tefferi A, Lasho TL, Finke CM, Knudson RA, Ketterling R, Hanson CH, et al. CALR vs JAK2 vs MPLmutated or triple-negative myelofibrosis: Clinical, cytogenetic and molecular comparisons. Leukemia. 2014;28(7):1472-7. PMid:24402162

Tefferi A, Wassie EA, Guglielmelli P, Gangat N, Belachew AA, Lasho TL, et al. Type 1 versus Type 2 calreticulin mutations in essential thrombocythemia: A collaborative study of 1027 patients. American Journal of Hematology. 2014;89(8):121-4.

Shirane S, Araki M, Morishita S, Edahiro Y, Takei H, Yoo Y, et al. JAK2, CALR, and MPL mutation spectrum in Japanese patients with myeloproliferative neoplasms. Haematologica. 2015; 100(2): e46-8. PMid:25398833 PMCid:PMC4803122

Murugesan G, Guenther-Johnson J, Mularo F, Cook JR, Daly TM. Validation of a molecular diagnostic assay for CALR exon 9 indels in myeloproliferative neoplasms: Identification of coexisting JAK2 and CALR mutations and a novel 9 bp deletion in CALR. International Journal of Laboratory Hematology. 2016;38(3):284-97. PMid:27018326

Broséus J, Lippert E, Harutyunyan AS, Jeromin S, Zipperer E, Florensa L, et al. Low rate of calreticulin mutations in refractory anaemia with ring sideroblasts and marked thrombocytosis. Leukemia. 2014;28(6):1374-6. PMid:24476766

Cazzola M, Kralovics R. From Janus kinase 2 to calreticulin: The clinically relevant genomic landscape of myeloproliferative neoplasms. Blood. 2014;123(24):3714-9. PMid:24786775

Kang MG, Choi HW, Lee JH, Choi YJ, Choi HJ, Shin JH, et al. Coexistence of JAK2 and CALR mutations and their clinical implications in patients with essential thrombocythemia. Oncotarget. 2016;7(35):57036-49. PMid:27486987 PMCid:PMC5302971

Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, et al. Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSETthrombosis). Blood. 2012;120(26):5128-33. PMid:23033268

Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: A international study. Journal of Clinical Oncology. 2011;29(23):3179-84. PMid:21747083

Tefferi A, Vainchenker W. Myeloproliferative neoplasms: Molecular pathophysiology, essential clinical understanding, and treatment strategies. Journal of Clinical Oncology. 2011;29(5):573-82. PMid:21220604

Thiele J, Kvasnicka HM, Müllauer L, Buxhofer-Ausch V, Gisslinger B, Gisslinger H. Essential thrombocythemia versus early primary myelofibrosis: A multicenter study to validate the WHO classification. Blood. 2011;117(21):5710-8. PMid:21447832


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Received 2022-07-14
Accepted 2023-11-08
Published 2023-12-19