Maine Children’s Hospital Archives - Hyundai Hope On Wheels

2014

Scholar Grant

Dr. Pradeep Sathyanarayana

Scarborough, ME

Acute myeloid leukemia (AML) refers to a heterogeneous group of malignancies with marked variability in their pathobiological features and clinical responses to therapy. According to Surveillance Epidemiology and End Results (SEER) cancer statistics review, approximately 20% of childhood leukemias are of myeloid origin and they represent a spectrum of hematopoietic malignancies. Approximately 14,590 people will be diagnosed with acute myeloid leukemia (AML) in 2013 and 10,370 will die from their disease. Among them, AML rates were reported to be highest in the first 2 years of life, but subsequently decreased with a lowest point at approximately 9 years of age. AML is a cancer that starts inside bone marrow, the soft tissue inside bones that helps form blood cells. This cancer grows from cells that would normally turn into white blood cells. Accumulation of several genetic changes or mutations in the cell that leads to increased or decreased levels of key regulatory proteins drives this pathological process. Recent evidence suggests that AML originates via the accumulation of mutations in a subset of early blood-forming cells termed “leukemia stem cells”. Identification and targeting of cancer stem cells is an emerging challenge in cancer biology. Once hidden in the genomic matter, microRNAs have emerged as important factors in cancer pathophysiology, including leukemia stem cells. In this proposal, I will investigate a microRNA called miR-199b, which we recently discovered it to be silenced in the bone marrow cells of AML patients. Importantly, low levels of this microRNA predict poor survival among AML patients. Successful completion of the proposed experiments will provide critical new insights into the impact of this microRNA on both the pathogenesis and targeted treatment of AML. Ultimately, it may be possible to target leukemia stem cells using miRNA-based therapeutics that build on data generated by the proposed research.