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Protein Identified that Drives Leukemia

Published: 2017-10-03 |

Source: Massachusetts General Hospital

A team lead by Massachusetts General Hospital investigators has identified a new cancer-causing pathway behind most cases of an aggressive type of leukemia, findings that could lead to new targeted treatment approaches. In the report published online in Cancer Discovery, the team describes finding a protein called TOX (thymocyte selection-associated high mobility box protein) that acts in concert with other oncogenes to initiate the development of T-cell acute lymphoblastic leukemia (T-ALL). Expressed in 95 percent of human T-ALL cases, TOX is also required for the cancer's growth and persistence.

"Despite the ability of front-line chemotherapy to induce remission in T-ALL, in many patients the cancer either does not respond to treatment or relapses after a first remission," says Davis Langenau, PhD, of the MGH Molecular Pathology Unit and the MGH Cancer Center, senior author of the report. Sadly, 70 percent of children and more than 90 percent of adults with treatment-resistant or relapsed T-ALL eventually succumb to their disease. Treatment resistance remains the greatest clinical challenge, which makes identifying common mechanisms that drive cancer growth a major imperative."

"A major role for TOX in T-ALL is to elicit defects in DNA repair leading to genetic changes that drive normal cells into cancer," says Dr. Langenau, PhD. "TOX then continues to be expressed within leukemic cells and is required for continueed tumor growth. That means that, if we can successfully target TOX with small molecules in the future, the 95 percent of T-ALL patient whose tumors express TOX would have new treatment options for this aggressive leukemia." In addition to better understanding how TOX regulates the continued growth of T-ALL, it also will be important to determine whether related TOX proteins have similar cancer-causing molecular functions in other types of cancers.

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