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The resistance fighter

Annual Report - Annual Report - Winter 2014

By Hilary Graham

Historically, research and patient care have been kept separate or “siloed.” Guillermo Garcia-Manero wants to change that.

An expert in blood cancers and translational medicine, Garcia-Manero, M.D., professor in Leukemia, notes that patients with myelodysplastic syndromes (MDS), in which the bone marrow doesn’t produce enough blood cells, often build a resistance to frontline drugs such as hypomethylating agents.

Garcia-Manero, M.D.
Photographer: Wyatt McSpadden

In turn, these patients develop acute myeloid leukemia (AML), which happens when there aren’t enough mature blood cells to prevent anemia, infection or bleeding. Hypomethylating agents, which target DNA, eliminate rapidly dividing cells without harming normal ones.

Through MD Anderson’s AML/MDS Moon Shot, Garcia-Manero is uncovering the molecular basis for the development of resistance to these agents. In other words, he’s seeking to discover what changes occur when the patient's body resists a drug and it stops working.

Understanding these changes is critical, according to Garcia-Manero, because resistance to hypomethylating agents also correlates with resistance to other drugs and, ultimately, poor patient prognosis

Unlike the genome, the presence and activity of proteins vary in each cell to support its unique functions. Garcia-Manero anticipates that identifying changes in protein type, levels and modifications in cells — a process called proteomic analysis — will reveal biomarkers that predict sensitivity, response and/or resistance to drugs. It also may uncover targets for new therapies.

MD Anderson Leukemia Center

  • Largest leukemia program in the world
  • Internationally known physicians
  • More than 150 active clinical trials
  • Access to investigational agents

48,610 people diagnosed with leukemia in the U.S. in 2013

  • 15,680 cases of chronic lymphocytic leukemia
  • 14,590 cases of acute myeloid leukemia
  • 6,070 cases of acute lymphocytic leukemia
  • 5,920 cases of chronic myeloid leukemia
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