Genetically Encoded Sensor Isolates Hidden Leukemic Stem Cells

Your right hand, Hashem, glorious in power, Your right hand, Hashem, shatters the foe! Exodus 15:6 (The Israel Bible™)

Leukemic stem cells are the most malignant of all leukemic cells. Understanding how leukemic stem cells are regulated has become an important area of cancer research.

Leukemia is a cancer of the white blood cells (leukocytes) in the blood. Stem cells are cells that can renew themselves by dividing and producing the same type of stem cells or can differentiate into other types of cells.

Now a team of researchers at Tel Aviv University has created a unique biosensor that can isolate and target leukemic stem cells. The research team was led by Dr. Michael Milyavsky of the pathology department at TAU’s Sackler School of Medicine. In a study published recently in the journal Leukemia, the team described their genetically encoded sensor, which has the ability to identify, isolate and characterize leukemic stem cells.

“The major reason for the dismal survival rate in blood cancers is the inherent resistance of leukemic stem cells to therapy,” Milyavsky noted. But only a minor fraction of leukemic cells has high regenerative potential, and it is this regeneration that results in the relapse of the disease. Until now, a lack of tools to specifically isolate leukemic stem cells has prevented the comprehensive study and specific targeting of these stem cells from occurring, he continued.

Malignant stem cells, which are typically rare and possess properties that are different from most other tumor cells, are the source of several types of human cancer. Because they target both healthy and leukemic cells, most chemotherapy drugs are not effective against them.

Until recently, cancer researchers used markers on the surface of the cell to distinguish leukemic stem cells from other cancer cells – but with only limited 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,” Milyavsky said.

“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 scientists searched genomic databases for “enhancers,” the specific regulatory regions of the genome that are particularly active in stem cells. Then they harnessed genome engineering to develop a sensor composed of a stem cell active enhancer fused with a fluorescence gene that labels the cells in which the enhancer is active.

“Using this sensor, we can perform personalized medicine oriented to drug screens by barcoding 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,” the TAU pathologist concluded. “We’re also interested in developing killer genes that will eradicate specific leukemia stem cells in which our sensor is active.” The researchers are now investigating those genes that are active in leukemic stem cells in the hope finding druggable target.