Acute myeloid leukemia (AML) is a deadly malignancy of the white blood cells that has few effective targeted treatments.

Professor Christopher Vakoc of Cold Spring Harbor Laboratory (CSHL) and former graduate student Sofya Polyanskaya discovered that AML cells rely on a previously unknown protein known SCP4 for survival. They found that this disease could be treated in a new way.

SCP4 is a phosphatase, which controls cell activity by removing phosphates from other proteins. The phosphates are re-attached by a protein called a kinase. The phosphorylation level of a protein, or the amount of phosphates added or withdrawn from it, regulates its activity.

Polyanskaya observed that SCP4 might interact with either STK35 or PDIK1L, two related kinases. The phosphatase and kinase appear to be required for AML cells to survive; shutting off the gene that makes SCP4 kills the cancer cells.

Polyanskaya was stunned to find only 12 studies in the scholarly literature that even reference SCP4. None of the studies mentioned the role of these proteins in cancer.

She says: “When you encounter something that was never previously studied in the context of cancer or hasn’t been understood at all, it’s very interesting.”

The researchers believe SCP4 is in charge of a critical metabolic process that AML cells rely on. SCP4-targeting drugs could starve and kill cancer cells while allowing healthy blood cells to thrive. Fortunately, medicines have previously been successful in targeting other phosphatases.

Polyanskaya admits that deciding to study SCP4 was risky.

Polyanskaya agrees that studying SCP4 was a risky decision. But now its essential role in AML cells has been found, Polyanskaya adds, “Other researchers can use this system and tweak some other things to really try and pinpoint the exact pathway. This work underscores the importance of fundamental research for discovering future therapies.”

Source: 10.1016/j.celrep.2021.110233

Image Credit: CSHL/2018

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