Expression of several critical hematopoietic regulator genes was altered by cohesin haploinsufficiency, though these effects were dependent on which fusion protein was present.
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Results: Serial plating assays demonstrated that cohesin haploinsufficiency increased colony forming capacity of cells expressing RC protein and decreased colony forming capacity of cells expressing CS protein. Transduced cells were then plated in methylcellulose with stem and myeloid-promoting cytokines for serial plating assays or transplanted into lethally irradiated recipient mice to assess effects on leukemic transformation. We used retroviral transduction to express either empty vector control, RC fusion, or CS fusion proteins. We hypothesized that loss of normal cohesin function enhances proliferation of cells expressing the RUNX1-CBFA2T1 (RC) fusion protein characteristic of t(8 21) AML and inhibits the proliferative capacity of cells expressing the CBFß-SMMHC (CS) fusion characteristic of inv(16) AML.ĭesign/Method: Bone marrow cells were harvested from mice with normal cohesin ( Smc3 +/+) or cohesin haploinsufficiency ( Smc3 +/-). Objectives: The goal of this project is to define how cohesin mutations alter the biology of core binding factor AML. Mutations in cohesin complex genes occur commonly in t(8 21) AML but are never found in inv(16) AML, suggesting a unique role of cohesin in the pathophysiology of each core binding factor AML subtype. Although these rearrangements are considered favorable risk in AML, nearly 30% of children with core binding factor AML will relapse, indicating a continued need for improved understanding of AML biology and new therapeutic targets. Shannon Conneely, Jason Rogers, Matthew Miller, Jason Guo, Rohit Gupta, Geraldo Medrano, Debananda Pati, Rachel Rauīaylor College of Medicine/Texas Children's Hospital, Houston, Texas, United Statesīackground: Core binding factor acute myeloid leukemia (AML) is a common type of pediatric AML characterized by inv(16) or t(8 21) lesions that inhibit the function of the core binding factor complex. Plenary Paper # 2001|||IMPACT OF ALTERED COHESIN FUNCTION ON PROLIFERATION OF CORE BINDING FACTOR ACUTE MYELOID LEUKEMIA
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