Abstract
Estrogen receptor (ER) signaling has been widely studied in a variety of solid tumors, where the differential expression of ERα and ERβ subtypes can impact prognosis. ER signaling has only recently emerged as a target of interest in acute myeloid leukemia (AML), an aggressive hematological malignancy with sub-optimal therapeutic options and poor clinical outcomes. In a variety of tumors, ERα activation has proliferative effects, while ERβ targeting results in cell senescence or death. Aberrant ER expression and hypermethylation have been characterized in AML, making ER targeting in this disease of great interest. This review describes the expression patterns of ERα and ERβ in AML and discusses the differing signaling pathways associated with each of these receptors. Furthermore, we assess how these signaling pathways can be targeted by various selective estrogen receptor modulators to induce AML cell death. We also provide insight into ER targeting in AML and discuss pending questions that require further study.
Highlights
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults, accounting for approximately 21,000 new diagnoses annually in the U.S [1]
A recent study showed that the enhancement of apoptosis by quercetin may partly be caused by the inactivation of DNA methylases resulting from the proteasomal degradation of class I histone deacetylases (HDACs), which leads to increased histone acetylation in the promotor regions of pro-apoptotic genes [86]
Not regarded as a sex-hormone-related disease, epidemiological and preclinical studies provide compelling data to support Estrogen receptor (ER) targeting in acute myeloid leukemia (AML)
Summary
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults, accounting for approximately 21,000 new diagnoses annually in the U.S [1] It is an aggressive hematological malignancy characterized by the accumulation of immature myeloid cells in the blood and bone marrow that impairs normal hematological and immune functions [2]. Selective estrogen receptor modulators (SERMs), a class of compounds that interact with ERs, have been studied for their effects in treating AML. This review summarizes these findings and provides an overview of the preclinical success of various SERMS
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