The impact of UBTF Tandem Duplications in Pediatric Acute Myeloid Leukemia

Dr. lannis Aifantis, Ph.D. – New York University Grossman School of Medicine, New York, NY

Acute myeloid leukemia (AML) is a type of blood cancer caused by genetic mutations in the stem cells residing in the bone marrow. AML in children is a serious disease, with only approximately half surviving. Recently, scientists have discovered a new genetic change in a gene named UBTF mainly found in children and young adults. This genetic change (UBTF-TD) is associated with a more aggressive form of AML with a worse survival rate (approximately 40% in 3 years). UBTF-TD often occurs with other common genetic mutations (especially the genes FLT3 and WT1). To better understand how UBTF-TD leads to AML combined with or without WT1/FLT3 mutations, we studied bone marrow samples from patients with specific genetic changes. We used state-of-the-art sequencing techniques to decipher the gene expression, genetic changes, and DNA accessibility to the protein regulators within each cell. Our initial findings suggest that UBTF-TD and its mutational combinations affect the way that the immune system interacts with the cancer cells and also modify critical upstream regulatory pathways. We believe that the UBTF-TD mutation may start the cancer process, and the FLT3/WT1 mutations worsen it by changing the behavior of the affected cells. Our research aims to uncover precisely how these genetic changes work together to drive pediatric AML. It also proposes and tests new drug treatments that can target this oncogenic event (UBTF-TD), hopefully leading to novel curative drug combinations.