{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:45:21Z","timestamp":1787503521515,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004595","name":"Universiti Sains Malaysia","doi-asserted-by":"publisher","award":["1001\/PPSP\/8070011"],"award-info":[{"award-number":["1001\/PPSP\/8070011"]}],"id":[{"id":"10.13039\/501100004595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Mutations of JAK2V617F, CALR, and MPL genes confirm the diagnosis of myeloproliferative neoplasm (MPN). This study aims to determine the genetic profile of JAK2V617F, CALR exon 9 Type 1 (52 bp deletion) and Type 2 (5 bp insertion), and MPL W515 L\/K genes among Malaysian patients and correlate these mutations with clinical and hematologic parameters in MPN. Mutations of JAK2V617F, CALR, and MPL were analyzed in 159 Malaysian patients using allele-specific polymerase chain reaction, including 76 polycythemia vera (PV), 41 essential thrombocythemia (ET), and 42 primary myelofibrosis (PMF) mutations, and the demographics of the patients were retrieved. The result showed that 73.6% JAK2V617F, 5.66% CALR, and 27.7% were triple-negative mutations. No MPL W515L\/K mutation was detected. In ET and PMF, the predominance type was the CALR Type 1 mutation. In JAK2V617F mutant patients, serum LDH was significantly higher in PMF compared to PV and ET. PV has a higher risk of evolving to post PV myelofibrosis compared to ET. A thrombotic event at initial diagnosis of 40.9% was high compared to global incidence. Only one PMF patient had a CALR mutation that transformed to acute myeloid leukemia. JAK2V617F and CALR mutations play an important role in diagnostics. Hence, every patient suspected of having a myeloproliferative neoplasm should be screened for these mutations.<\/jats:p>","DOI":"10.3390\/ijerph18147582","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T10:52:58Z","timestamp":1626432778000},"page":"7582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Clinical and Laboratory Features of JAK2 V617F, CALR, and MPL Mutations in Malaysian Patients with Classical Myeloproliferative Neoplasm (MPN)"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2760-0703","authenticated-orcid":false,"given":"Razan Hayati","family":"Zulkeflee","sequence":"first","affiliation":[{"name":"Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia"},{"name":"Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2029-2234","authenticated-orcid":false,"given":"Zefarina","family":"Zulkafli","sequence":"additional","affiliation":[{"name":"Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia"},{"name":"Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6344-0220","authenticated-orcid":false,"given":"Muhammad Farid","family":"Johan","sequence":"additional","affiliation":[{"name":"Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azlan","family":"Husin","sequence":"additional","affiliation":[{"name":"Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia"},{"name":"Department of Internal Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5937-6473","authenticated-orcid":false,"given":"Md Asiful","family":"Islam","sequence":"additional","affiliation":[{"name":"Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0493-1390","authenticated-orcid":false,"given":"Rosline","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia"},{"name":"Hospital Universiti Sains Malaysia, Kubang Kerian 16150, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1182\/blood-2016-10-696005","article-title":"Myeloproliferative neoplasm stem cells","volume":"129","author":"Mullally","year":"2017","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1056\/NEJMra1406186","article-title":"Myeloproliferative Neoplasms","volume":"376","author":"Spivak","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1056\/NEJMoa1716614","article-title":"Classification and Personalized Prognosis in Myeloproliferative Neoplasms","volume":"379","author":"Grinfeld","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5254","DOI":"10.1002\/cam4.2387","article-title":"Two activating mutations of MPL in triple-negative myeloproliferative neoplasms","volume":"8","author":"Xie","year":"2019","journal-title":"Cancer Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pizzi, M. (2021). Crossing the borders: An integrated approach to myeloproliferative neoplasms and mastocytoses. Cancers, 13.","DOI":"10.3390\/cancers13071492"},{"key":"ref_6","first-page":"397","article-title":"Prevalence of MPL (W515K\/L) Mutations in Patients with Negative-JAK2 (V617F) Myeloproliferative Neoplasm in North-East of Iran","volume":"13","author":"Shams","year":"2018","journal-title":"Iran. J. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"735","DOI":"10.3892\/ol.2014.2801","article-title":"Detection of JAK2 V617F mutation increases the diagnosis of myeloproliferative neoplasms","volume":"9","author":"Zhang","year":"2015","journal-title":"Oncol. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"370","DOI":"10.3892\/br.2017.977","article-title":"Prevalence of the janus kinase 2 V617F mutation in philadelphia-negative myeloproliferative neoplasms in a portuguese population","volume":"7","author":"Azevedo","year":"2017","journal-title":"Biomed. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1182\/blood-2017-06-782037","article-title":"Myeloproliferative neoplasms: From origins to outcomes","volume":"130","author":"Nangalia","year":"2017","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Machado-Neto, J.A., Campos, P.d., and Trainaen, F. (2018). CALR (calreticulin). Atlas Genet. Cytogenet. Oncol. Haematol.","DOI":"10.4267\/2042\/68172"},{"key":"ref_11","first-page":"1","article-title":"CALR mutations in a cohort of JAK2 V617F negative patients with suspected myeloproliferative neoplasms","volume":"9","author":"Mikic","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Grabek, J., Straube, J., Bywater, M., and Lane, S.W. (2020). MPN: The Molecular Drivers of Disease Initiation, Progression and Transformation and their Effect on Treatment. Cells, 9.","DOI":"10.3390\/cells9081901"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_14","unstructured":"Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., and Thiele, J. (2017). World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues Revised, International Agency for Research on Cancer (IARC). [4th ed.]."},{"key":"ref_15","unstructured":"QIAGEN Group (2010). QIAsymphony DNA Handbook, Forest Stewardship Council (FSC)."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zakaria, N.A., Rosle, N.A., Asmaa, M.J.S., Aziee, S., Haiyuni, M.Y., Samat, N.A., Husin, A., Hassan, R., Ramli, M., and Yusoff, S.M. (2021). Conformation sensitive gel electrophoresis for the detection of calreticulin mutations in BCR-ABL1-negative myeloproliferative neoplasms. Int. J. Lab. Hematol.","DOI":"10.1111\/ijlh.13628"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Heppner, J., Nguyen, L.T., Guo, M., Naugler, C.F., and Rashid-Kolvear, F. (2019). Incidence of myeloproliferative neoplasms in Calgary, Alberta, Canada. BMC Res. Notes, 12.","DOI":"10.1186\/s13104-019-4321-1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13045-016-0242-9","article-title":"Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): Analysis from the German SAL-MPN-registry","volume":"9","author":"Kaifie","year":"2016","journal-title":"J. Hematol. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5461","DOI":"10.1182\/blood-2018-99-114416","article-title":"Myeloproliferative Neoplasms in Asia, Including Middle East, Turkey, and Algeria: Epidemiological Indices and Treatment Practice Patterns from the Multinational, Multicenter, Observational MERGE Registry","volume":"132","author":"Yassin","year":"2018","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1309\/AJCPALP51XDIXDDV","article-title":"The prevalence of JAK2, MPL, and CALR mutations in Chinese patients with BCR-ABL1-Negative Myeloproliferative Neoplasms","volume":"144","author":"Lin","year":"2015","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"41","DOI":"10.31557\/APJCP.2019.20.1.41","article-title":"Polycythaemia vera among Sudanese patients with special emphasis on JAK2 mutations","volume":"20","author":"Ibrahim","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"882","DOI":"10.3346\/jkms.2015.30.7.882","article-title":"JAK2 V617F, MPL, and CALR mutations in Korean patients with essential thrombocythemia and primary myelofibrosis","volume":"30","author":"Kim","year":"2015","journal-title":"J. Korean Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1093\/ajcp\/aqw005","article-title":"Myeloproliferative neoplasms with calreticulin mutations exhibit distinctive morphologic features","volume":"145","author":"Loghavi","year":"2016","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/S1726-4901(10)70115-5","article-title":"Prevalence of MPL W515L\/K Mutations in Taiwanese Patients With Philadelphia-negative Chronic Myeloproliferative Neoplasms","volume":"73","author":"Lieu","year":"2010","journal-title":"J. Chin. Med. Assoc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s43042-019-0039-9","article-title":"MPL W515 L\/K mutations in myeloproliferative neoplasms","volume":"20","author":"Eldeweny","year":"2019","journal-title":"Egypt. J. Med. Hum. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8","DOI":"10.4274\/tjh.65807","article-title":"Kronik miyeloproliferatif neoplazmlarda MPL W515L\/K mutasyonlari","volume":"30","author":"Akpinar","year":"2013","journal-title":"Turk. J. Hematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4650","DOI":"10.1177\/0300060518787719","article-title":"Correlation analysis between JAK2, MPL, and CALR mutations in patients with myeloproliferative neoplasms of Chinese Uygur and Han nationality and their clinical characteristics","volume":"46","author":"Lang","year":"2018","journal-title":"J. Int. Med. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"209","DOI":"10.4103\/IJPM.IJPM_223_17","article-title":"Molecular genetics of BCR-ABL1 negative myeloproliferative neoplasms in India","volume":"61","author":"Rabade","year":"2018","journal-title":"Indian J. Pathol. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1182\/asheducation-2016.1.534","article-title":"Update from the latest WHO classification of MPNs: A user\u2019s manual","volume":"2016","author":"Passamonti","year":"2016","journal-title":"Hematology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1002\/ajh.24578","article-title":"Molecular testing for JAK 2, MPL, and CALR in myeloproliferative neoplasms","volume":"91","author":"Xia","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1007\/s12185-016-2050-y","article-title":"Usefulness of spleen volume measured by computed tomography for predicting clinical outcome in primary myelofibrosis","volume":"104","author":"Song","year":"2016","journal-title":"Int. J. Hematol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Iurlo, A., Cattaneo, D., Bucelli, C., and Baldini, L. (2020). New perspectives on polycythemia vera: From diagnosis to therapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165805"},{"key":"ref_33","unstructured":"Ashorobi, D., and Gohari, P. (2020). Essential Thrombocytosis, StatPearls Publishing."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1136\/jclinpath-2018-205227","article-title":"Essential thrombocythaemia with mutation in MPL: Clinicopathological correlation and comparison with JAK 2V617F-mutated and CALR- mutated genotypes","volume":"71","author":"Arenillas","year":"2018","journal-title":"J. Clin. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.hemonc.2014.12.002","article-title":"The mutation profile of JAK2, MPL and CALR in Mexican patients with Philadelphia chromosome-negative myeloproliferative neoplasms","volume":"8","year":"2015","journal-title":"Hematol. Oncol. Stem Cell Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/modpathol.2012.165","article-title":"Development of monocytosis in patients with primary myelofibrosis indicates an accelerated phase of the disease","volume":"26","author":"Boiocchi","year":"2013","journal-title":"Mod. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4249","DOI":"10.1182\/blood.V128.22.4249.4249","article-title":"Monocytosis Is a Powerful and Independent Predictor of Shortened Overall and Leukemia-Free Survival in Primary Myelofibrosis","volume":"128","author":"Shah","year":"2016","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41408-018-0054-y","article-title":"The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: Document summary and in-depth discussion","volume":"8","author":"Barbui","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.3324\/haematol.2010.026708","article-title":"Comparison of different criteria for the diagnosis of primary myelofibrosis reveals limited clinical utility for measurement of serum lactate dehydrogenase","volume":"95","author":"Beer","year":"2010","journal-title":"Haematologica"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1093\/ajcp\/aqw131","article-title":"Laboratory Investigation of Myeloproliferative Neoplasms (MPNs)","volume":"146","author":"Busque","year":"2016","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41408-017-0024-9","article-title":"Marked elevation of serum lactate dehydrogenase in primary myelofibrosis: Clinical and prognostic correlates","volume":"7","author":"Shah","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12885-019-5387-9","article-title":"A systematic review and meta-analysis of the prevalence of thrombosis and bleeding at diagnosis of Philadelphia-negative myeloproliferative neoplasms","volume":"19","author":"Rungjirajittranon","year":"2019","journal-title":"BMC Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1515\/tjb-2020-0267","article-title":"Relationship between JAK2-V617F mutation and hematologic parameters in Philadelphia-negative chronic myeloproliferative neoplasms","volume":"45","author":"Aksit","year":"2020","journal-title":"Turkish J. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chia, Y.C., Ramli, M., Woon, P.Y., Johan, M.F., Hassan, R., and Islam, M.A. (2021). Molecular genetics of thrombotic myeloproliferative neoplasms: Implications in precision oncology. Genes Dis.","DOI":"10.1016\/j.gendis.2021.01.002"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40164-018-0124-7","article-title":"The epidemiology and clinical characteristics of myeloproliferative neoplasms in Malaysia","volume":"7","author":"Yap","year":"2018","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_46","first-page":"33","article-title":"A sensitive detection method for MPLW515L or MPLW515K mutation in myeloproliferative disorders","volume":"4","author":"Chi","year":"2014","journal-title":"Euro. J. Exp. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3343\/alm.2016.36.4.291","article-title":"Screening PCR versus sanger sequencing: Detection of CALR mutations in patients with thrombocytosis","volume":"36","author":"Jeong","year":"2016","journal-title":"Ann. Lab. Med."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/14\/7582\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:30:46Z","timestamp":1760164246000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/14\/7582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,16]]},"references-count":47,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ijerph18147582"],"URL":"https:\/\/doi.org\/10.3390\/ijerph18147582","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,16]]}}}