Investigation of miRNAs in Patients with JAK2+ Chronic Myeloproliferative Neoplasia and Conversion to JAK2+ Secondary Myelofibrosis

Chronic Myeloproliferative Neoplasms (CMPNs) are clonal hematopoietic disorders characterized by the proliferation of mature myeloid cells and the development of bone marrow fibrosis. CMPNs include disease groups such as Philadelphia chromosome-negative Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (PMF). These conditions are more common in older patients, with the average age of diagnosis for ET, PV, and PMF being between 53-60 years. More than 90% of CMPN patients have driver mutations in genes encoding Janus Kinase 2 (JAK2), Calreticulin (CALR), or thrombopoietin receptor (MPL). PV and ET can progress to Secondary Myelofibrosis over time, with fibrotic transformation seen in 12-21% and 9-10% in PV and ET, respectively. Secondary Myelofibrosis is characterized by factors such as advanced age, leukocytosis, anemia, high LDH levels, splenomegaly, ASXL1 mutations, and JAK2V617F allele mutation. Studies have shown that epigenetic mechanisms, especially miRNAs, play a role in the development of CMPNs. Our study aimed to investigate the effect of miR-135a-5p on the transformation of JAK2+ CMPNs into JAK2+ Secondary Myelofibrosis. We collected blood samples from 40 patients diagnosed with CMPN at Istanbul University-Cerrahpaşa, Cerrahpaşa Medical Faculty Hospital and from 10 age- and gender-matched healthy individuals as a control group. After isolating plasma from peripheral blood, we extracted miRNA and then converted the samples into cDNA. The expression of miRNA-135a-5p was analyzed using the real-time polymerase chain reaction (RT-PCR) method. Our results showed that miR-135a-5p expression increased by 43% in patients with PV and by approximately 50% in patients with ET + PV compared to controls and that miR-135a-5p behaved like an oncomiR in these patients. Finally, we showed that miR-135a-5p expression was associated with smoking (p=0.056) and glucose levels (p=0.021) in patients with PV. Harmful substances in cigarettes and glucose levels may affect miRNA expression and promote cancer formation.