What Research Tells Us About Sex-Based Differences in AML Outcomes

There is a small but significant gap in survival between men and women with Acute Myeloid Leukemia (AML). Research has shown that males diagnosed with AML have worse outcomes than females despite receiving the same types of treatment. In an effort to understand why this gap exists, researchers looked at different sex-based hormones and sex-based characteristics and how they are related to AML outcomes. 

Hormone signaling in AML

Hormone signaling refers to the way that hormones communicate between cells. This influences the ways that cells carry out specific functions in the body, like metabolism and protective responses. 

In AML, immature cells called blasts multiply quickly and prevent healthy cells from functioning properly. High androgen receptor (AR) expression in AML has been linked to poor survival. 

An androgen is a type of hormone produced in higher levels among males, however both males and females have these hormones in their bodies.The most well-known of these is testosterone. Androgen receptors are proteins that bind to these male hormones.   

A research study designed to explore hormone expression on AML cells looked at whether androgen protected cancerous cells from chemotherapy and led to worse outcomes.

The study found that AML cells in both men and women express high levels of androgen receptors. However, they also found that when AML cells were exposed to male hormones in a lab, there was no impact on how the cells grew or responded to chemotherapy. Similarly, evaluation of the expression of estrogen, a sex hormone produced much higher in females, showed no impact on the health and function of cells or response to treatment.

This means that differences in sex hormone signaling between males and females are not the cause of the disparities in outcomes.

Inflammation may impact cell growth and function more than hormones

Even though AML cells express high levels of androgens, these do not appear to impact whether the leukemia grows or responds to treatment. Instead, the study showed that inflammation may have more impact on outcomes than the male hormones.  

Additional research is needed to better understand the biological factors that influence sex-based outcomes in AML, such as:  

• Drug metabolism 
• Immune response
• Mutation patterns

Understanding the underlying biological factors that influence cell activity can improve diagnosis, treatment, and overall outcomes for people with AML.  

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Sources: 

• Acute myeloid leukaemia cells express high levels of androgen receptor but do not depend on androgen signaling for survival 
• Androgen receptor signaling as a new target for intervention in acute myeloid leukemia 
• National Cancer Institute-Androgen Receptor Definition