To Evaluate the Role of Estrogen Receptor in Myeloid Leukemia

Abstract

The malignancy of white blood cells (WBCs) is called leukemia. Leukemia is divided into acute and chronic myeloid leukemia based on its rate of growth. Acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML) that is principally defined by t (15; 17), a balanced translocation that results in the fusion of the PML/RAR fusion gene, account for 10-15% of newly diagnosed acute myeloid leukemia. Chronic Myeloid Leukemia occurs due to the Philadelphia chromosome which was first identified as a truncated version of chromosome 22 and later as a t (9;22) translocation. All-trans Retinoic Acid, Arsenic Trioxide, chemotherapy, and combinations are now used to treat APL. The emergence of resistance, differentiation syndrome, and ATO toxicity makes these treatments less effective. Tyrosine kinase inhibitors (TKIs) have marked a ground-breaking finding in the treatment of CML. However, it became resistant to imatinib, which now requires special attention. The role of Endocrine signaling, specifically that of estrogen receptor (ER) is very significant in progression of different cancers and has been linked to Wnt/Beta Catenin pathway which is indispensable for APL and CML. We therefore wanted to learn more about how endocrine signaling functions in APL (NB4) and CML (K562) mice. We demonstrated that NB4 and K562 are negative for ER and PR utilizing in silico, biochemical, and pharmacological techniques. Fulvestrant showed off target effects on our models Our results suggest that Fulvestrant interferes with proliferation of NB4 and K562 cells by downregulating Wnt target genes including c-myc (p-value < 0.001) and axin 2 (p-value < 0.01) in both AML and CML. In conclusion our results suggest that Fulvestrant also targets other potential candidates which show its off-target activity and need to be further explored in different AML and CML models.