# Acute myeloid leukaemia cells express high levels of androgen receptor but do not depend on androgen signaling for survival

## TL;DR

Men with acute myeloid leukemia have worse outcomes than women, but androgen signaling in cancer cells does not appear to be the reason.

## Contribution

AML cells express high androgen receptor levels, but androgen signaling does not support their survival or resistance to treatment.

## Key findings

- Men with AML had lower remission rates and worse survival than women.
- AML cells showed high androgen receptor expression, but androgens did not affect their survival or chemotherapy resistance.
- Estrogen signaling also had no impact on AML cell survival in experiments.

## Abstract

Male sex is associated with worse outcome in acute myeloid leukemia (AML) in many studies. We analyzed the survival of 4281 patients treated with intensive chemotherapy in the AML17 and AML19 trials based on sex. Men had a significantly lower remission rate than women. Men had a higher incidence of adverse cytogenetic features and a lower incidence of the relatively favorable NPM1 mutation. However, male sex was an independent risk factor for survival in multi-variate analysis. We hypothesized that androgen signaling in men could worsen outcomes by protecting AML cells from chemotherapy. We demonstrated high levels of androgen receptor (AR) expression in AML across cytogenetic risk groups. We showed the AR expression was induced by IL-6 signaling in vitro and correlates with poor overall survival. Androgens had no effect on survival of primary AML cells in vitro, nor did they impact gene expression. Androgens did not protect AML cells against chemotherapy either in vitro or in vivo. Similar results were observed with estrogen signaling through estrogen receptor in vitro in AML cells. In conclusion, targeting the androgen pathway may not be a promising clinical strategy and sex hormone signaling in AML cells does not explain the poorer outcomes of men.