Role of Ikaros in Tumor Suppression in Leukemia
Open Access
- Author:
- Bhalodia, Riya
- Area of Honors:
- Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Sinisa Dovat, Thesis Supervisor
Sairam V Rudrabhatla, Thesis Honors Advisor
Nik Tsotakos, Faculty Reader - Keywords:
- Ikaros
Acute Lymphoblastic Leukemia
ALL
R-loops
epigenetic regulation - Abstract:
- Ikaros is a zinc finger protein encoded by gene IKZF1 and is an important transcription factor for the maturation of T and B lymphocytes. Clinically, Ikaros has been found to be one of the most relevant tumor suppressors in acute lymphoblastic leukemia (ALL). Genome wide analyses on large cohorts of ALL patients have shown Ikaros is frequently mutated in these cases. While research has associated Ikaros deletions to the occurrence of ALL, the regulatory mechanisms that control cellular proliferation in ALL remain unclear. Therefore, elucidating the molecular mechanisms through which Ikaros contributes to ALL pathogenesis can provide a step towards improved treatment of these high-risk ALL patients. Research has linked genomic instability to the development of leukemia. In cells, genomic instability is often induced by R-loops, a triple-stranded DNA-RNA hybrid structure. We looked at the effect of Ikaros on formation of R-loops to gain insight into how Ikaros mediates gene expression in leukemia. The hypothesis that Ikaros regulates the formation of R-loops was tested in Ikaros-null T-ALL cells and following re-introduction of Ikaros into those cells. The results of the conducted experiments demonstrated that restoration of Ikaros in DN3 cells reduces R-loops distribution.