Targeting the MLL1 gene as a form of cancer treatment for MLL1-Rearranged Leukemia

Advisor(s)

Dr. Crystal Randall, Illinois Mathematics and Science Academy

Location

Room A123

Start Date

26-4-2019 10:05 AM

End Date

26-4-2019 10:20 AM

Abstract

The Mixed Lineage Leukemia gene (MLL gene) is classified as a histone methyltransferase in the family of histone-modifying enzymes (Shilatifard 2012). It directly influences developmental regulation by controlling the gene expression necessary for embryonic and hematopoietic stem cell development (Shilatifard 2012). While the normal MLL1 gene, a member of the MLL gene family, functions in development, the mutated version has been found to lead to cancer.

With MLL1-rearranged leukemia, the first identified fusion partner of the MLL1 gene is TET1, a founding member of the TET family of enzymes. TET1 has shown to play an oncogenic role in the development of MLL1-rearranged leukemia by upregulating the transcription of the genes that are critical for the induction and maintenance of leukemia stem cells in MLL1-rearranged leukemia. Because TET1 plays an essential oncogenic role in MLL1-rearranged leukemia, there is potential for the TET1 gene to serve as a target in MLL1-rearranged leukemia treatment (Huang 2013). In this research, an altered epigenetic state has been initiated in MLL1-rearranged cells by inducing a TALE-TET1 fusion; by doing so, it was observed whether apoptosis increases in cells. The ultimate goal of this research is to evaluate the effectivity of epigenetic editing in treating MLL1-rearranged leukemia.

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Apr 26th, 10:05 AM Apr 26th, 10:20 AM

Targeting the MLL1 gene as a form of cancer treatment for MLL1-Rearranged Leukemia

Room A123

The Mixed Lineage Leukemia gene (MLL gene) is classified as a histone methyltransferase in the family of histone-modifying enzymes (Shilatifard 2012). It directly influences developmental regulation by controlling the gene expression necessary for embryonic and hematopoietic stem cell development (Shilatifard 2012). While the normal MLL1 gene, a member of the MLL gene family, functions in development, the mutated version has been found to lead to cancer.

With MLL1-rearranged leukemia, the first identified fusion partner of the MLL1 gene is TET1, a founding member of the TET family of enzymes. TET1 has shown to play an oncogenic role in the development of MLL1-rearranged leukemia by upregulating the transcription of the genes that are critical for the induction and maintenance of leukemia stem cells in MLL1-rearranged leukemia. Because TET1 plays an essential oncogenic role in MLL1-rearranged leukemia, there is potential for the TET1 gene to serve as a target in MLL1-rearranged leukemia treatment (Huang 2013). In this research, an altered epigenetic state has been initiated in MLL1-rearranged cells by inducing a TALE-TET1 fusion; by doing so, it was observed whether apoptosis increases in cells. The ultimate goal of this research is to evaluate the effectivity of epigenetic editing in treating MLL1-rearranged leukemia.