Molecular Signature Predicts Transition from Myelodysplastic Syndrome to Acute Myeloid Leukemia

Progress from myelodysplastic syndrome (MDS) to acute myeloid leukemia (AML) is linked to the enzyme glycogen synthase kinase, and a molecular signature predicts clinical outcomes of patients with MDS. These findings were published in Cancer Cell (doi:10.1016/j.ccell.2015.11.012).

"We've found that the transition from healthy to cancerous blood stem cells happens in clear, compartmentalized steps," said Mick Bhatia, PhD, director of the McMaster Stem Cell and Cancer Research Institute in Hamilton, Ontario, Canada, and principal investigator of the study. "We've identified 2 steps in that staircase."

MDS occurs when blood-forming cells in the bone marrow are damaged, leading to low numbers of 1 or more types of blood cells, according to the American Cancer Society. MDS transforms to AML in approximately one-third of patients; therefore, MDS is now classified as a form of cancer. Approximately 20 830 new cases of AML in adults are diagnosed each year, and the disease causes an estimated 10 460 deaths each year.

This new retrospective study examined genes for the alpha and beta forms of glycogen synthase kinase. If 1 form was deleted in hematopoietic stem cells, MDS was the result. However, when both forms were deleted, AML cancer developed.

These findings were tested in human blood samples from patients with MDS, some of whom later developed AML. The study demonstrated that the development of AML in patients could accurately be predicted by analyzing gene expression in patient blood samples.

Bhatia explained that the next step is to use this predictive gene expression as a target for drugs to prevent AML from developing altogether. Their research found that glycogen synthase kinase beta form interactions with Wnt/Akt/mTOR signaling and the alpha form affects metabolism, so these are likely potential targets for preventing disease evolution.

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