Mer inhibition may be key to enhanced leukemia treatment

Inhibition of the protein receptor Mer destroys cancer cells and makes chemotherapy more effective in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), two research projects indicated.

Abnormal tyrosine kinase activation in AML has been associated with poor prognosis and provides strategic targets for novel therapy development, explained the authors of one study in the journal Oncogene. Doug K. Graham, MD, PhD, of the University of Colorado Cancer Center in Denver, and colleagues found that the Mer receptor tyrosine kinase was overexpressed in a majority of pediatric (29 of 36, or 80%) and in all adult (10 of 10) primary AML patient blasts at the time of diagnosis, and in all patient samples at the time of relapse. Mer was also found in 12 of 14 AML cell lines (86%). In contrast, normal bone marrow myeloid precursors expressed little to no Mer.

The Mer receptor sits within the cell membrane. Once the receptor is activated, the cell receives signals to grow and survive. When Graham's group stopped Mer production in leukemia cells, leukemia cell death increased significantly, as did leukemia cells' sensitivity to chemotherapy. In addition, survival improved in mouse models of the disease. 

Graham also was involved in the other study, this one published in Blood Cancer Journal (2013;3:e101). This work, which focused on ALL, the most common pediatric cancer, showed abnormal expression of Mer receptor tyrosine kinase in approximately half of pediatric T-cell leukemia patient samples and T-cell ALL (T-ALL) cell lines. Similarly promising results from inhibition of the Mer protein receptor were seen: Once again, this act increased the sensitivity of the leukemia cells to chemotherapy, decreased the oncogenic potential of T-ALL cell lines, and significantly increased median survival in a mouse model of leukemia, from 30.5 days to 60 days.

The findings suggest that Mer inhibition may be the key to less toxic, more effective therapies for leukemia.

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