Publication Date

2017-06-14

Availability

Embargoed

Embargo Period

2019-06-14

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Cancer Biology (Medicine)

Date of Defense

2017-05-05

First Committee Member

Izidore S. Lossos

Second Committee Member

Wasif Noor Khan

Third Committee Member

Robert B. Levy

Fourth Committee Member

Ralf Landgraf

Fifth Committee Member

Jaime R. Merchan

Abstract

LMO2 serves as one of the best prognostic markers for longer survival of diffuse large B cell lymphoma (DLBCL) patients. However, little it is known about its molecular function in normal B cells and DLBCL cells. Our study reveals a novel role for LMO2 in the control of DNA repair. We found that LMO2 inhibits the homologous recombination repair pathway, an essential mechanism for the repair of DNA double-strand breaks (DSB). The lack of activity of the homologous recombination pathway causes an accumulation of DSB in LMO2 expressing B cells, thus providing explanation for increased chemo-sensitivity of LMO2+ DLBCL tumors and the improved survival rates observed in patients with these tumors. Furthermore, based on our studies, here we propose a new treatment for LMO2-expressing DLBCL based on the observed DNA repair deficiency using Poly (ADP-ribose) polymerase (PARP) inhibitor-mediated synthetic lethality approach.

Keywords

diffuse large B cell lymphoma; LMO2; DNA repair

Available for download on Friday, June 14, 2019

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