Mar 13 2019
Stem cells have been noted to multiply, proliferate, and differentiate. As a result of these qualities, leukemic stem cells are said to be highly malignant of all leukemic cells. Therefore, getting an insight into how leukemic stem cells are controlled has become a crucial area of cancer study.
(Image credit: Tel Aviv University)
Researchers at Tel Aviv University (TAU) have developed a unique biosensor that can isolate and target leukemic stem cells. The research team, headed by Dr Michael Milyavsky of the Department of Pathology at TAU's Sackler School of Medicine, explains their unique genetically encoded sensor and its capacity to identify, isolate, and define leukemic stem cells in a study published in the January 31st issue of Leukemia.
The major reason for the dismal survival rate in blood cancers is the inherent resistance of leukemic stem cells to therapy. But only a minor fraction of leukemic cells have high regenerative potential, and it is this regeneration that results in disease relapse. A lack of tools to specifically isolate leukemic stem cells has precluded the comprehensive study and specific targeting of these stem cells until now.
Dr. Michael Milyavsky, Department of Pathology, Sackler School of Medicine, TAU.
Until now, cancer scientists used markers on the surface of the cell to differentiate leukemic stem cells from the bulk of cancer cells, with only narrow success. "There are hidden cancer stem cells that express differentiated surface markers despite their stem cell function. This permits those cells to escape targeted therapies," Dr. Milyavsky explains. "By labeling leukemia cells on the basis of their stem character alone, our sensor manages to overcome surface marker-based issues.
"We believe that our biosensor can provide a prototype for precision oncology efforts to target patient-specific leukemic stem cells to fight this deadly disease."
The researchers combed genomic databases for "enhancers," the particular regulatory regions of the genome that are mostly active in stem cells. Then they harnessed genome engineering to create a sensor made up of a stem cell active enhancer attached with a fluorescence gene that tags the cells in which the enhancer is active.
The researchers were also able to show that sensor-positive leukemia stem cells are sensitive to a recognized and low-cost cancer drug called 4-HPR (fenretinide), offering a novel biomarker for patients who can possibly gain from this drug.
Using this sensor, we can perform personalized medicine oriented to drug screens by barcoding a patient's own leukemia cells to find the best combination of drugs that will be able to target both leukemia in bulk as well as leukemia stem cells inside it. We're also interested in developing killer genes that will eradicate specific leukemia stem cells in which our sensor is active.
Dr. Michael Milyavsky, Department of Pathology, Sackler School of Medicine, TAU.
The scientists are currently examining those genes that are active in leukemic stem cells in the expectation of locating druggable targets.