Researchers at the University of Colorado Cancer Center studying a gene that causes childhood leukemia have discovered a way to make hematopoietic stem cells (HSCs) that could be used in the treatment of blood cancer.
There has been considerable research into stem cells for use in treating blood cancers such as leukemia. If stem cells are transplanted into patients after chemotherapy has been used to kill cancerous cells, they can develop into healthy cells; however, there is a problem. Induced pluripotent stem cells (IPSCs) can differentiate into healthy cells but they can also develop into cancer. HSCs are a safer option as they can form certain types of blood cell and will not develop into cancer, but it has not been possible to create HSCs that take hold and grow in the body.
The researchers were studying a gene called MLL, which can cause childhood leukemia when it fuses with another gene. In order to investigate the role of MLL in leukemia, the researchers needed to know how the gene functioned in healthy individuals. The team split into two groups, one studying the role of MLL in leukemia and the other studied the normal functioning of the MLL gene.
“When we knocked out this (MLL) gene, we saw that hematopoietic stem cells couldn’t retain their ‘stemness’ – instead of being HSCs, they would differentiate to become like normal cells of the blood system. So, we wondered what would happen if we increased it,” said Patricia Ernst, PhD, CU Cancer Center investigator and Professor in the CU School of Medicine Departments of Pediatrics.
The researchers doubled the amount of the protein MLL in pluripotent stem cells and the cells were able to produce more blood cells. This could greatly improve treatments for patients with leukemia, as it may be possible to use the stem cells to regrow a patient’s blood system after radiation therapy or chemotherapy has been used to kill the cancer cells.
The researchers were able to study the differentiation process using single-cell sequencing. “As pluripotent cells differentiate, they enter a kind of transitional state in which they still have the potential to become many different cell types. Single-cell sequencing let us watch the fate of these transitional cells, and we saw that activating MLL led to more of these transitional cells becoming blood cell types,” explained Ernst.
Ernst and her team are planning further research to identify potential drugs that can amplify the level of MLL to help patients grow blood cells after cancer treatment. The ultimate goal is to develop customizable stem cells products that can be used to treat any patient, rather than having to reply on stem cell donors.
You can read more about the study in the paper – Enhancing Hematopoiesis from Murine Embryonic Stem Cells through MLL1-Induced Activation of a Rac/Rho/Integrin Signaling Axis – which was recently published in Stem Cell Reports. DOI: 10.1016/j.stemcr.2019.12.009