Gene Signature Developed As Predictive and Prognostic Biomarker for Acute Myeloid Leukemia Treatment

A 17 gene signature has been identified by the research team from the Princess Margaret Centre from stem cells that can be used to diagnose whether patients suffering from acute myeloid leukemia will respond to treatment. Dr. Jean Wang who is the Affiliate Scientist at the Princess Margaret, University Health Network (UHN) said that the gene signatures could be used as a risk assessment tool to determine the individual response and the course of treatment that would suit treatment.

Personalized Medicine

Personalized medicine is growing in popularity and tests are being developed to assess personal response to treatment and medications. Such gene marker tests are routinely used to determine the need for intensive therapies like chemotherapy. The tests determine the recurrence risk for cancer and if the recurrence risk is low, then chemotherapy may not be advised.

Advantages

• Doctors will get a better understanding about the type of cancer.
• The recurrence risk of cancer can be determined.
• It will identify response to medicines.

LSC17 Score

The new biomarker LSC17 score has the following factors

• This biomarker is derived from leukemia stem cells that are responsible for driving disease.
• Chemotherapy is resisted by these dormant cells.
• This is the underlying factor for return in cancer during remission.

The benefit of using the LSC17 score is that patients who are found to be resistant to the standard form of chemotherapy will easily be identified by physicians. This will aid in

• Avoiding side effects and trauma incurred due to chemotherapy.
• It will avoid wasting time and resources on standard chemotherapy measures.
• Newer adaptive techniques that are novel or post remission therapies can be used for such patients to control the growth of cancer.

Cancer Cells in Acute Myeloid Leukemia

Acute myeloid leukemia was one of the first diseases in which it was determined that the disease was sustained by leukemia stem cells. This was identified when it was found that not all leukemia cells had the ability to proliferate indefinitely, which was determined by growing the leukemia cells in- vitro. Only a small fraction of cells was found to grow in colonies.

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Leukemia stem cells that give rise to AML were evaluated by isolating these cells and injecting them into immune-deficient mice which helped in identifying that these cells resulted in the development of cancer.

In AML, the leukemic blasts that rapidly divide are eliminated by chemotherapeutics but the leukemia stem cells are resistant to chemotherapy and radiation, due to the microenvironment of the bone marrow. They remain in the body and there is regrowth of the cancer cells, resulting in a very short period of remission.

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Stemness Score

The LSC17 score was determined by studying the leukemia samples from 78 acute myeloid leukemia patients along with their gene expression patterns. The researchers in the study then determined the stemness score using statistical methods.

Stanley W. K. Ng, who is the co-author of the study said 㜁e identified the minimal set of genes that were most critical for predicting survival in these other groups of AML patients, regardless of where they were treated. With this core 17-gene score, we have shown we can rapidly measure risk in newly diagnosed AML patients,"

Interpretation of the Score

Low ScoreCancer would respond well to chemotherapy and there is a low chance of remission.

High Score Cancer will not respond well to stand forms of therapy even after a stem cell transplantation.

The method of determining the score has been converted into a platform called Nanostring that will aid in quicker turn around. This will aid the score from being used widely in the clinical set up.

Dr. Wang further added "The LSC17 score is the most powerful predictive and prognostic biomarker currently available for AML, and is the first stem cell-based biomarker developed in this way for any human cancer. Clinicians will now have a tool that they can use upfront to tailor treatment to risk in AML."

Acute Myeloid Leukemia

This type of cancer is characterized by the production of abnormal myelocytes in the bone marrow, red blood cells or platelets. The initial symptoms associated with the condition include fever, easy bruising, feeling of being tired and bleeding. This cancer should be detected early as it increases in intensity very fast.

The pathogenesis of this type of cancer is due to the over production of white blood cells in the bone marrow which result in poor numbers of red blood cells and platelets. As the number of these immature cells increase, they begin to circulate in the blood and since they are immature, they cannot perform their functions well. This lowers their immunity and it can lead to poor defense against infection.

The current study will aid in identifying the line of treatment that will be effective and the prognosis of the patient.

References:

1. Acute myeloid leukaemia (AML) - (https://www.cancer.gov/types/leukemia/patient/adult-aml-treatment-pdq)
2. General Information About Adult Acute Myeloid Leukemia - (http://www.leukaemia.org.au/blood-cancers/leukaemias/acute-myeloid-leukaemia-aml)

Source-Medindia