Overexpression of MicroRNA-125b Causes and Progresses Leukemia

The National Cancer Institute estimates that more than 43,000 people will be diagnosed in the United States with some form of leukemia leading to nearly 22,000 people losing their lives in 2010.

The ailment is commonly known as blood cancer. Here, malignant rogue cells grow in an uncontrollable fashion posing threat to the existence of healthy cells by outnumbering them. Either cells of the immune system become lower in number or the blood cell count is decreased. The result is decrease in the immune capabilities of the body or a fatal condition called anemia.

Now, researchers at the Whitehead Institute have discovered that “overexpression of the microRNA 125b (miR-125b)” can be a reason behind the origin of several types of leukemia and in accelerating the progression of the ailment.

The results of their study were published in the online edition of the journal, the Proceedings of the National Academy of Sciences (PNAS), on the last week of November 2010. The study was supported by the National Institutes of Health (NIH), Association pour la Recherche sur le Cancer (ARC) and the Leukemia and Lymphoma Foundation.

Basics to Appreciate the Research Findings: According to the central principle of Biology, the basic building blocks of life are cells which follow instructions for their functioning known as genes. These genes are chemical structures made up of DNA molecules.

RNAs are the molecules which read these instructions called genes and produce chemicals called proteins which carry out the functions of cells eventually. For some uncontrollable reasons when the position of the molecules in the genes change, the process is called mutation. Change in the structure alters the functionality of cells too.

Knowledge Gained from the Research on the MicroRNA 125b (miR-125b) Over-expression:

  • It was a known fact to the researchers that the levels of microRNAs are high in many cancers.
  • The researchers wanted to learn whether this very reason can be the cause of the disease’s origin or not in laboratory mice and in humans.
  • Cancer disease is caused as such when genetic mutations (or changes in chemical structure of genes) cause healthy cells to turn malignant.
  • Very little is known on the subject of mutations which cause blood cancer and its several types.
  • The researchers selected a less explored mutation which leads to over-expression of miR-125b RNAs in some blood cancer patients.
  • These RNAs are associated with functioning of genes which regulate the process of programmed cell death (apoptosis).
  • The study found that mutation of the interest here changed the expression of the microRNA 125b by 90 times compared to its normal expression.
  • To check whether over-expression of this RNA can cause blood cancer on its own, the researchers injected fetal liver cells into laboratory mice which increased the production of miR-125b.
  • There were extremely high levels of this RNA produced in the mice after a period of 16 weeks.
  • In between 12 and 29 weeks, 50 percent of the transplanted mice lost their lives from B-cell acute lymphoblastic leukemia, myeloproliferative neoplasm or T-cell acute lymphoblastic leukemia which are different types of blood cancers.
  • The next step in the research was to prove whether the RNA played a role in the rapid progression of the disease.
  • The researchers transplanted bone marrow cells in the laboratory mice with mutation which overproduced miR-125b.
  • The rats with this transplantation survived for 21 days when compared to the rats without this mutation which survived for 35 days.

Conclusion: The research study proved that miR-125b over-expression can cause blood cancer and also rapidly progress the ailment. Though the genes associated with miR-125b are yet to be identified, the researchers believe that these genes play a role in the fast growth of rogue cells and their early maturation.

Further studies of the research work will be focused on identification of the many target genes of miR-125b. Any development in this field can open up doors for single and novel treatment for many leukemia types.

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