The effects of mutational profiles on phenotypic presentation of myeloproliferative neoplasm subtypes in Bosnia: 18 year follow-up

Amina Kurtovic-Kozaric; Erna Islamagic; Hana Komic; Nurija  Bilalovic; Izet Eminovic; Adnan Burekovic; Amna Uzunovic; Sabira Kurtovic

doi:10.17305/bjbms.2019.4391

Authors

Amina Kurtovic-Kozaric Department of Clinical Pathology, Cytology and Human Genetics, Clinical Center of the University of Sarajevo, Sarajevo, Bosnia and Herzegovina; Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0002-6063-7260
Erna Islamagic Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0002-1785-5035
Hana Komic Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0001-5209-393X
Nurija Bilalovic Department of Clinical Pathology, Cytology and Human Genetics, Clinical Center of the University of Sarajevo, Sarajevo, Bosnia and Herzegovina
Izet Eminovic Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0001-9392-3215
Adnan Burekovic Department of Internal Medicine, Clinical Hospital, Zenica, Bosnia and Herzegovina https://orcid.org/0000-0002-0152-6050
Amna Uzunovic Department of Internal Medicine, Clinical Hospital, Zenica, Bosnia and Herzegovina https://orcid.org/0000-0001-9707-3537
Sabira Kurtovic Department of Hematology, Clinical Center of the University of Sarajevo, Sarajevo, Bosnia and Herzegovina https://orcid.org/0000-0003-1353-3634

DOI:

https://doi.org/10.17305/bjbms.2019.4391

Keywords:

MPN, myeloproliferative neoplasm, JAK2, janus kinase 2, CALR, calreticulin, MPL, myeloproliferative leukemia virus, mutant allele burden

Abstract

The identification of mutually exclusive somatic mutations shared among myeloproliferative neoplasm (MPN) subtypes has provided a powerful tool for studying disease evolution. Clinical features, gene mutations, and survival over 18 years were analyzed in MPN patients. One hundred thirty-eight MPN patients were subcategorized according to MPN subtypes: essential thrombocythemia (ET, n = 41), polycythemia vera (PV, n = 56), primary myelofibrosis (PMF, n = 10), and MPN unclassified (MPN-U, n = 31). Patient characteristics included clinical parameters, overall survival (OS), and mutational status of the Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukemia virus oncogene (MPL) genes. We compared hematologic and clinical features of JAK2^V617F-ET vs. CALR-mutated ET vs. JAK2^V617F-PV patients. JAK2^V617F-patients had higher values of erythrocytes, hemoglobin, and hematocrit compared to CALR-mutated patients (p < 0.05). The mutant allele burden in JAK2^V617F-PV and JAK2^V617F-ET patients directly correlated with erythrocyte, hemoglobin, and hematocrit values, but it inversely correlated with platelet count. Thus, mutant allele burden was an indicator of the clinical phenotype in JAK2^V617F-MPN patients. OS was not affected by the mutational status. In general, mutated JAK2, CALR, and MPL genes left specific hematological signatures.