FEATURES OF HEMATOLOGICAL PARAMETERS IN CALR-POSITIVE PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS

Poluben L., Neumerzhitska L., Verbylenko R., Shumeiko O., Klymenko S.

MEDICAL GENETICS

Scentific article

Classic chronic Ph-negative myeloproliferative neoplasms (MPNs) are an unique group of hematologic diseases encompassing polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Our understanding of the mechanisms of MPNs development was dramatically changed in 2005, when recurrent mutation of tyrosine kinase JAK2V617F was described in most patients with PV and in 50-60% patients with ET and PMF. Later, other MPNs-causing mutations were reported in MPL, CALRgenes as well as in JAK2gene involving other localizations. In most cases mutations in these genes arise in mutually exclusive way and cause establishment of myeloproliferative phenotype predominantly through JAK-STAT3/5 signalling pathway. Therefore, MPNs have common molecular genetic features and can mimic each other. However, due to impact of the factors such as specific disease-causing mutations in one of three mentioned genes, experiencing of low doses of ionizing radiation, they can present with different clinical characteristics. Aim of our research was to study the frequency of the most common CALRgene mutations and their association with clinical hematological characteristics in Ukrainian patients with ET and PMF with accent on radiation-associated MPNs. 144 patients with ET and PMF (including 42 patients who were previously exposed to low doses of ionizing radiation) were tested for presence of JAK2V617F mutation using allele-specific PCR, 1 st type CALR(52 bp deletion) and 2 nd type CALR(5 bp insertion) gene mutations using RT-PCR. Hematological parameters in 144 MPN patiens were analysed. CALR gene mutations were detected in 26 (18,1%) cases, including 12 (28,6%) patient with MPNs previously exposed to ionizing radiation. In our study we showed that CALRgene mutations are more common among MPN patients who were previously exposed to ionazing radiation (p = 0,05). Platelets count is higher (p = 0,0004), but red blood cells count (p = 0,04) and level of hemoglobin (p = 0,05) are lower in CALR-positive patients, than in JAK2-positive patients.

myeloproliferative neoplasm, mutation, CALR, JAKV617F

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«Bulletin of problems biology and medicine» Issue 1 Part 1 (142), 2018 year, 227-230 pages, index UDK 591.156:575.113:616-005.6:616.155.191

10.29254/2077-4214-2018-1-1-142-227-230