Haleh Yaghoubi, Nastaran Yegani, Sara Falahati, Narges Firouzpour, Neda Zahmatkesh

, Sina Mirzaahmadi, Golnaz Asaadi Tehrani
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Abstract
Chronic Myeloid Leukemia (CML) is a complex haematological malignancy characterized by abnormal myeloid cell proliferation. Long non-coding RNAs (lncRNAs) have gained attention for their roles in cancer, including CML. Our study investigates the expression patterns of lncRNAs NEAT1, EMG3, FENDRR, and HULC in K562 CML cells under various drug treatments. We explored the impact of chemotherapy agents hydroxycarbamide, cyclophosphamide, cytarabine, and thiosemicarbazone complexes on lncRNA expression. Cyclophosphamide treatment resulted in significant upregulation of NEAT1, EMG3, and HULC, while HULC exhibited downregulation at lower concentrations and longer durations. Hu treatment led to consistent upregulation of FENDRR and HULC, indicating concentration-dependent responses. Combined CP and Arac treatment showed concentration-dependent effects on lncRNAs, with NEAT1 and EMG3 displaying optimal responses at specific concentrations and durations. Complex drug treatments yielded diverse outcomes. NEAT1 responded positively to Complex 1 but negatively to Complex 3. EMG3 showed marked upregulation under Complex 3. FENDRR and HULC exhibited variable expression changes under different concentrations and durations, emphasising the intricate regulatory dynamics. Thiosemicarbazone Ni and Cu treatments had concentration-dependent effects on lncRNA expression. NEAT1, EMG3, and HULC displayed sensitivity to specific concentrations and durations, highlighting their potential responsiveness to these treatments. Our findings provide insights into the dynamic expression of lncRNAs in response to drug treatments in CML. Understanding these regulatory mechanisms may pave the way for targeted therapeutic interventions in CML, optimising treatment strategies for improved patient outcomes.