CAMBRIDGE, Mass. (November 29, 2010) Whitehead Institute researchers have shown in mouse models that overexpression of the microRNA 125b (miR-125b) can independently cause leukemia and accelerate the disease's progression. Their results are published in this week's online edition of the Proceedings of the National Academy of Sciences (PNAS).
"MicroRNAs are elevated in many cancers, but in humans and mice, can upregulation of a microRNA actually cause the cancer? That's the question," says Whitehead Institute Founding Member Harvey Lodish. "This 22 nucleotide RNA, one of the smallest RNAs in the body, apparently causes leukemia when it's overexpressed."
According to estimates from the National Cancer Institute, more than 43,000 people in the United States will be diagnosed with some form of leukemia in 2010 and approximately 22,000 will die from the disease. In leukemia, one type of blood cell divides in an uncontrolled fashion in the bone marrow, crowding out other blood cells and frequently causing lowered immunity, anemia, and organ damage.
Leukemias are differentiated by the cell type that hyperproliferates, be it a cell from the lymphoid lineage (B or T-cell) or the myeloid lineage that give rise to red cells, platelets or myeloid cells.
Like other cancers, leukemia is caused by genetic mutations that alter how cells divide, proliferate, or mature. Some leukemia-causing mutations, like the BCR-ABL gene fusion, are relatively well-studied, but little is known about many leukemia-causing mutations.
In the PNAS paper, first author Marina Bousquet examined a less-studied mutation that leads to miR-125b overexpression in some leukemia patients.
MicroRNAs, like miR-125b, are very short pieces of RNA that normally fine-tune the activity of their target genes. Some miR-125b targets have already been described, including genes involved in the P53 pathway. These targets, which were found by Lodish's former grad
|Contact: Nicole Giese|
Whitehead Institute for Biomedical Research