First decoding of the CD34 stem cell genome in lymphoma: Opening the way for targeted treatment
In recent years, lymphoma research has gradually shifted from symptom treatment towards understanding the “root causes” of the disease at the cellular and genetic levels. In Vietnam, a group of scientists from the Institute of Biology under the Vietnam Academy of Science and Technology, led by Assoc. Prof., Dr. Nguyen Thi Xuan, carried out the research project entitled: “Studying the role of several genes regulating the functions of CD34+ stem cells and dendritic cells for lymphoma treatment” (code: TĐTBG0.05/21-23).
One of the highlights of the study was genome sequencing performed on CD34+ stem cells. The research team identified numerous genetic variants directly related to lymphoma, notably genes such as NCF1, MMP9, VDR and especially CNN2 and MUC4, which appeared at high frequencies in patients. These findings help provide a clearer genetic picture of the disease, which still contains many gaps, particularly among Vietnamese patients.
The study also showed that when the CNN2 and MUC4 genes operate at low levels, the disease tends to progress more severely, accompanied by signs such as increased inflammatory responses or abnormalities in blood indices. This opens up the possibility of using these genes as “early warning signals”, helping doctors identify high-risk patient groups in order to adopt more suitable treatment approaches.
Experiment separating bone marrow mononuclear cells for the isolation of CD34 stem cells
Notably, the study demonstrated that the A20 gene acts as a “switch” regulating immune cell activity. When this gene functions abnormally, the ability of dendritic cells and macrophages to recognise and destroy cancer cells is significantly affected. Conversely, if the activity of the A20 gene can be adjusted, the effectiveness of cancer cell elimination may be improved.
Analysis of genetic variants using whole-exome sequencing techniques
Another notable discovery was the difference in the effects of chemotherapy drugs. Certain drugs such as Doxorubicin not only destroy cancer cells but also “activate” the immune system to participate in the process. When combined with drugs targeting signalling pathways such as Everolimus, treatment effectiveness may be enhanced in patients with specific genetic abnormalities. In addition, the study also clarified the role of the CNN2 gene in regulating the activity of dendritic cells, one of the immune system’s key “warriors”.
Assoc. Prof. , Dr Nguyen Thi Xuan stated that the team had successfully built an exome genome database of 30 Vietnamese lymphoma patients. This database is considered an important resource for domestic genetic research and precision medicine. The successful isolation, cultivation and mastery of CD34+ stem cells and dendritic cells with high survival rates have created a solid experimental foundation for more in-depth studies. In particular, the team identified the regulatory roles of genes such as A20, CYLD and CNN2 in immune activity and disease progression, while also establishing a gene-editing process using CRISPR-Cas9 technology - an important step forward opening the possibility of personalised therapeutic intervention.
Translated by Tuyet Nhung
Link to Vietnamese version
