George Adrian Calin. M.D., Ph.D. University of Texas MD Anderson Cancer Center

GENETICS

Roles of microRNA in familial chronic lymphocytic leukemia

Update:

As a starting point, we used the well-described peculiarity that family members of CLL patients also develop CLL or other types of cancer much more frequently than to be expected by chance. We propose that the responsible genes, at least for a portion of the patients, are genes recently identified and named microRNAs (miRNAs).

Research performed during the first 18 months of the grant maintains the view that these very small genes could play an important role in the initiation of familial CLL. We identified that in familial cases the malignant cells with miRNAs were deleted or mutated. We have also shown that inserting the missing genes into the malignant cells decreases the potential of formation of leukemic cells. We have also pioneered the idea that miRNAs, and other larger non-codingRNAs, named ultraconserved genes, are involved in the formation and production of tumors, particularly in leukemias and lymphomas. These results offered the genetic basis for performing laboratory studies aimed at understanding the therapeutic potential of these miRNAs in patients with familial form of CLL.

The broad, long-term purpose of my research is to decipher the roles of non-codingRNAs, including miRNAs, in the initiation and progression of blood cancers. The final results will reveal new markers for molecular diagnosis and prognosis of blood cancers, such as CLL, and new targets for drug therapy.