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.
