Cell Surface Molecule Found to Promote Acute Myeloid Leukemia Growth

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CD98 molecule could be a potential therapeutic target in AML.

One of the challenges when it comes to treating cancer is treatment resistance. However, in a new study, researchers discovered that the cell surface molecule CD98 promotes acute myeloid leukemia (AML) and the findings may lead to new therapeutic options.

AML is cancer of the blood and bone marrow and, according to 2016 estimates from The American Cancer Society, there will be approximately 19,950 new cases of AML and about 10,430 deaths as a result. Furthermore, AML is known for its drug resistance and relapse.

To address this issue, researchers set out to determine CD98’s role in AML for a study published in Cancer Cell.

CD98 is a molecule found on the surface of cells and controls how cells stick to one another. CD98 levels have been known to be higher in some solid tumors and are linked to poor prognosis. The molecule is also known to play a role in the proliferation and activation of certain immune cells.

“To improve therapeutic strategies for this disease, we need to look not just at the cancer cells themselves, but also at their interactions with surround cells, tissues, molecules, and blood vessels in the body,” said co-senior study author Tannishtha Reya, PhD. “In this study, we identified CD98 as a critical molecule driving AML growth. We should that blocking CD98 can effectively reduce leukemia burden and improve survival by preventing cancer cells from receiving support from the surrounding environment.”

For the study, researchers used engineered mouse models that lacked CD98 to determine its role in AML. They found that the loss of CD98 not only blocked AML growth but also improved survival. Since the absence of CD98 allowed normal blood cells to be left alone, the findings indicated its potential as a therapeutic option.

Upon further investigation, researchers found that leukemia cells that lacked CD98 had fewer stable interactions with the lining of blood vessels. These interactions are necessary for the growth of AML.

The researchers then tested to see what would happen if they used a deliverable inhibitor to blocked block CD98 in AML. They used the humanized antibody called IGN523 in their AML models.

The results showed that IGN523 blocked CD98’s AML promoting activity in the laboratory human cells and in the AML mouse models. Additionally, researchers transplanted human derived AML cells into mice and treated them soon after with IGN523 or with a control antibody.

These found thatIGN523 was able to effectively eliminate AML cells, while the AML in the control mice increased more than 100-fold.

“This study suggests that human AML can’t get established without CD98, and that blocking the molecule with anti-CD98 antibodies could be beneficial for the treatment of AML in both adults and children,” Reya said.

The authors noted that they will continue their researcher to find out if CD98 could be targeted to treat pediatric AML.

“Many of the models we used in this work were based on mutations found in childhood AML,” Reya said. “While many childhood cancers have become very treatable, childhood AML continues to have a high rate of relapse and death. We plan to work with pediatric oncologists to test if anti-CD98 agents can be effective against pediatric AML, and whether it can improve responses to current treatments. I think this is particularly important to pursue since the anti-CD98 antibody have already been through phase 1 trials, and could be more easily positioned to test in drug-resistant pediatric AML.”

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