Health
NUS researchers develop new approach to predict resistance to cancer treatments
Understanding coexistence of oncogenes in hematologic malignancies
By directing the production of ‘bad’ oncoproteins that promote cancer growth and survival, oncogenes play an important role in cancer development and simultaneously influence treatment outcomes. However, cancers often express multiple such oncogenes, and not all cancer cells express all oncogenes. Because oncogenes are typically studied one at a time, little is known about how the ‘coexistence’ of oncogenes in subsets of cancer cells affects the survival of cancer patients.
To fill this knowledge gap, the research team set out to figure out if and how oncogenes work together to resist therapy and studied the phenomenon in the context of DLBCL.
In current clinical practice, immunohistochemistry is routinely used to measure three specific oncogenes (MYC, BCL2, and BCL6) to identify high-risk cases of DLBCL. However, immunohistochemistry is unable to detect these three oncogenes simultaneously, thus failing to identify subgroups of cells with specific oncogenic combinations. To overcome this challenge, the team used a state-of-the-art imaging technique called multispectral microscopy with quantitative immunofluorescence to simultaneously stain, image and quantify these oncogenes in numerous samples from DLBCL patients.
unfavorable combination
The researchers found that patients with a high percentage of cells that were positive for MYC and BCL2 but negative for BCL6 had poorer survival. The presence of these types of cells results in the lowest viability compared to other cell combinations for the three oncogenes, including those positive for all three. Based on this important finding, the researchers concluded that BCL6 plays a ‘protective’ role by ‘suppressing’ aggressive cells harboring both MYC and BCL2 oncogenes. They then identified a potential mechanism why BCL6 “protects” cells with high MYC and BCL2.
The research team also used immunohistochemistry data to develop a formula that “predicts” the percentage of cells with this particular harmful carcinogenic combination. The matter is currently being investigated further through an international collaboration led by a team at CSI Singapore.
Associate Professor Jeyasekaran, corresponding author of the study and principal investigator at CSI Singapore, said of the importance of the team’s research: Moreover, it may suggest a paradigm that can be applied to other types of cancers, in that simultaneous detection of oncogenes is essential for understanding their clinical relevance. ”
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