Divergent gene expression of PTGS1 and PTGS2 along the disease course of chronic myeloid leukaemia

Denise Kusma Wosniaki¹Bianca Nichele Kusma¹Anelis Maria Marin¹Eduardo Cilião Munhoz²João Samuel de Holanda Farias²Eduarda Batista Mendes¹Mateus Aoki¹Dalila Lucíola Zanette^1*

• ¹Carlos Chagas Institute (LaCTAS), Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil
• ²Hospital Erasto Gaertner, Curitiba, Paraná, Brazil

Chronic myeloid leukaemia (CML) is a chronic myeloproliferative disorder caused by the reciprocal translocation of chromosomes 9 and 22. This genetic abnormality leads to the uncontrolled proliferation of myeloid lineage cells, ultimately causing the leukaemia. Inflammation plays a significant role in the progression of various cancers, including lungs, colorectal, breast, head and neck, and haematological malignancies. Prostaglandins, which are key mediators in these processes, are synthesised by cyclooxygenases. Consequently, these genes are critical targets for studying CML due to their involvement in leukaemogenesis. In this study, we evaluated the expression of PTGS1 and PTGS2 in a cohort of peripheral blood samples from CML patients using qPCR and cell culture methodologies being evaluated by Kruskall-Wallis and simple linear regression statistical models. Our results showed increased expression of both PTGS1 and PTGS2 in patients with favorable prognosis, suggesting a correlation between inflammatory processes and CML. Notably, we observed lower expression of PTGS1 and PTGS2 in groups with uncontrolled CML (high BCR::ABL1 levels) compared to healthy controls (HCs), and with patients in treatment-free remission (TFR), or those undergoing treatment with imatinib The use of NSAIDs, however, did not impact significantly the expression of PTGS genes in our cohort. Additionally, PTGS1 and PTGS2 expression levels were evaluated in a CML cell line treated in vitro with Imatinib, which provided further evidence to the hypothesis that increased PTGS1 expression could be related to the good response to treatment in CML. These findings may suggest a potential influence of inflammatory pathways in CML, particularly related to the roles of COX-1 and COX-2 in leukaemogenesis and response to Imatinib.