Chromosomal Abnormalities in Chronic Lymphocytic Leukemia

Summary

This project explores the genetic and chromosomal factors contributing to CLL, the most common leukemia in Western countries. CLL is characterized by the abnormal proliferation of B-cells, often due to genetic mutations and chromosomal abnormalities such as deletions in 13q, 11q, and 17p, as well as Trisomy 12. These mutations disrupt critical genes like ATM, TP53, SF3B1, and NOTCH1, which play key roles in DNA repair, apoptosis, and cell cycle regulation. Mutations in TP53 and ATM are associated with treatment resistance and poor prognosis, especially when they co-occur, supporting the double-hit hypothesis. Mutations in SF3B1 affect mRNA splicing, while NOTCH1 mutations prolong oncogenic signaling, increasing disease aggressiveness and resistance to therapy. Environmental factors such as pesticide exposure and genetic predisposition further increase CLL risk. The study also highlights the role of the tumor microenvironment, where chemokines like CXCL12 and nurse-like cells (NLCs) contribute to CLL cell survival and proliferation. Understanding these genetic interactions and their contribution to CLL progression is crucial for developing targeted therapies, including CAR-T cell therapies and BCL-2 inhibitors, which offer promising avenues for more effective and personalized treatments.

Image shows how BCR recognizes antigens, and there is activation of proliferation and increased survival pathways
(Figure representation created by the author:Manasa Thiruppathi and Peiqun Zheng)

This image simplifies the NOTCH1 pathway, and shows how the mutated variant eventually leads to increased cell division.
(Figure representation created by the author:Manasa Thiruppathi and Peiqun Zheng)

Video Presentation

Impact Statement

This project dives into Chronic Lymphocytic Leukemia and the common patterns of chromosomal and genetic mutations observed in patients. During these weeks, I learnt a lot about cancer and its mechanisms, as well as research methods, how to read publications, and useful bioinformatic tools. Although the final report was written by my partner and I, I would like to convey my gratitude to my instructor and the entire team at ELIO who guided us through this process and helped tie it all together.

Impact Statement

The goal of this project was to research the cancerous disease, Chronic Lymphocytic Leukemia, and the genetic changes that make the disease worse. Although there are several other factors we found that worsened the disease such as epigenetic ones, we determined that through the two-hit hypothesis, a change where double genetic mutations are found on a gene and a section of the chromosome, certain “double-hits” cause the lifespan of a person to decrease dramatically. Through the ELIO program, I learned to research by using resources on the internet, and how to make our own research diagrams. I liked listening to the lectures, as they were intresting and very fun! The program will definitely he of help to me to future research because I now have a better understanding of how to conduct research within a timeframe, and how to present the main points of the research.

Report White Paper

(Click to view the full report)

By: Manasa Thiruppathi and Peiqun Zheng. The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of Elio Academy.

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