Leukemias are the most common pediatric cancers accounting for approximately 30% of total diagnoses. Although remarkably high cure rates have now been achieved for acute lymphoblastic leukemia (ALL), the risk of refractory or recurrent disease is significantly elevated in patients of Hispanic descent, a major demographic served by the UT Health San Antonio. The goal of the proposed study is to address this medical need by exploring a new paradigm for treatment of refractory/recurrent ALL and acute myeloid leukemia (AML). The study seeks to enhance the efficacy of cytarabine, a first-line treatment for AML and refractory/recurrent ALL, using a novel strategy suggested by two recent seminal st...

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Leukemias are the most common pediatric cancers accounting for approximately 30% of total diagnoses. Although remarkably high cure rates have now been achieved for acute lymphoblastic leukemia (ALL), the risk of refractory or recurrent disease is significantly elevated in patients of Hispanic descent, a major demographic served by the UT Health San Antonio. The goal of the proposed study is to address this medical need by exploring a new paradigm for treatment of refractory/recurrent ALL and acute myeloid leukemia (AML). The study seeks to enhance the efficacy of cytarabine, a first-line treatment for AML and refractory/recurrent ALL, using a novel strategy suggested by two recent seminal studies. The studies identified a new target for overcoming cytarabine resistance, SAMHD1, an enzyme that limits the concentration of the active metabolite of cytarabine in cancer cells. In this project we will discover small-molecule inhibitors of SAMHD1 that will be used for development of new medicines for treatment of AML and ALL. We will also test this new treatment paradigm in a unique collection of cancer models developed from biopsies obtained from pediatric AML and ALL patients in Texas.

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