Unlocking New Avenues in Multiple Myeloma Treatment: Targeting Anti-Apoptotic Genes to Enhance Drug Efficacy Open Access

Abstract

This study explored the role of Bcl-2 and Bcl-xL, anti-apoptotic genes known for promoting cancer cell survival, in the drug resistance of multiple myeloma by using CRISPR/Cas9 to knock them out in the KMS18 cell line. The efficacy of these knockouts was confirmed through Western blotting, and their impact on drug-induced apoptosis was assessed using Annexin-V and propidium iodide staining with flow cytometry, particularly in response to the proteasome inhibitor bortezomib. Results showed that knocking out these genes increased the susceptibility of multiple myeloma cells to apoptosis, underscoring their potential as therapeutic targets. Despite facing methodological challenges such as maintenance of cell lines and issues with co-immunoprecipitation reagents, the study offers valuable insights into overcoming drug resistance and improving treatment outcomes in multiple myeloma. Future research should investigate the combinatorial effects of these gene knockouts and develop in vivo models to further validate these findings, advancing personalized medicine in cancer treatment.

Table of Contents

INTRODUCTION

Characteristics of Cancer

Multiple Myeloma

Epidemiology Multiple Myeloma

Pathophysiology of Multiple Myeloma

Management and Treatment of Multiple Myeloma

Targeting Anti-Apoptotic Genes in Multiple Myeloma

METHODS

RESULTS

Figure 1. Western Blot Verification of Bcl-2 KO and Bcl-xL KO in KMS18 cell line.

Figure 2. First Trial of Dose-Curve Bortezomib with KMS18 Parental, Bcl-2 KO, and Bcl-xL KO cells.

Figure 3. Second Trial of Dose-Curve Bortezomib with KMS18 Parental, Bcl-2 KO, and Bcl-xL KO cells.

Figure 4. Third Trial of Dose-Curve Bortezomib with KMS18 Parental, Bcl-2 KO, and Bcl-xL KO cells.

Figure 5. Bim co-IP Actin and Bcl-xL.

DISCUSSION

REFERENCES

About this Honors Thesis

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Molecular Biology, Cell Biology, Genetics
Keyword	Multiple Myeloma Drug Treatment Apoptosis Cancer
Committee Chair / Thesis Advisor	Dr. Lawrence Boise, Emory University
Committee Members	Dr. LaTonia Taliaferro-Smith, Emory University Dr. Anita Corbett, Emory University

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