Can Genetic Information Present at Diagnosis Can Predict Relapse and Shape CML Treatment Planning?

Certain genetic characteristics of chronic myeloid leukemia (CML) can predict the likelihood that relapse will occur. Relapse is when the cancer comes back after treatment ends. Being able to understand a patient’s risk of relapse at the time of diagnosis can help doctors evaluate what treatments will be most effective for treating CML. 

CML occurs when genetic changes produce an enzyme called tyrosine kinase that promotes excessive growth of white blood cells.

A type of targeted therapy called trosine kinase (TKI) inhibitors are the main treatment for CML. It works by blocking tyrosine kinase enzymes and helping to stop the growth of cancer cells. 

However, some leukemic stem cells (LSC) that are difficult to isolate remain even after treatment with a TKI. This can lead to a relapse. 

Researchers have found significant differences in the leukemic stem cells of people who stay in remission versus those who experience relapse.  

Identifying biomarkers or biological characteristics that can predict meaningful clinical outcomes helps researchers understand how a disease develops and responds to treatment. 

A research study looking at relapse in CML used biomarkers to separate people who relapsed into two categories:

• Proliferative relapse, which is caused by rapid cell growth

• Immune relapse, which is caused by inflammatory signaling and cell adhesion

The LSCs found in bone marrow across both groups evaluated were SPAG6, PRSS21, and CD71. Each of these genes is abnormally expressed in CML and can contribute to relapse even after a person is treated with a TKI inhibitor. 

Additionally, some biomarker expression reduced over time and in some cases was not detectable in reduced-sensitivity testing. 

What does this mean for patients?

This research shows that relapse risk in CML may be identifiable at the time of diagnosis. Knowing the characteristics of these cells can also help in developing drugs that focus on specific targets when developing new treatments. Early and sensitive testing to establish what biomarkers are present can lead to more personalized treatment and better outcomes for people with CML. 

Studies like this rely on real-world health information to better understand disease patterns and treatment response. 

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Sources: 

•  A single-cell atlas of diagnostic bone marrow to uncover the origins of CML relapse following therapy cessation 
• NIH-Treatment-free Response 
• Cleveland Clinic- TKI 
• NIH-Biomarkers