New research from the University of Colorado Cancer Center has identified a way to make hematopoietic stem cells from a gene that causes a type of leukemia in children. The work was led by Patricia Ernst, Ph.D., CU Cancer Center investigator and professor in the CU School of Medicine Departments of Pediatrics, and was published recently in the journal Stem Cell Reports.
In fact, the discovery about hematopoietic stem cells (HSCs) came as quite a surprise for Ernst and her colleagues. She comments:
"My lab was working on a gene called MLL that, when accidentally fused together with another gene, causes childhood leukemia," says Ernst. "Half my lab was studying MLL's role in leukemia and the other half was exploring what MLL normally does," Ernst says. "When we knocked out this 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," Ernst says.
This observation led the team of researchers to analyze the function of MLL down to the cellular level. They concluded two key findings regarding the role the gene plays in stem cell differentiation and maintenance. First, they determined that increasing the amount of MLL protein in pluripotent stem cells triggers the cells to generate more blood cells, which has significant implications for leukemia patients recovering from chemotherapy and irradiation.
"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," Ernst says.
Second, the team discovered that the MLL gene and its cancer-causing cousin can be targeted individually, which could improve drug development against MLL-rearranged childhood leukemia. "It's about selective targeting," Ernst says. "We want to selectively turn off the cancer-causing MLL fusion gene without affecting the regular form of the MLL gene."
Ernst and her colleagues aim to continue their investigations in order to develop a drug-based method to augment MLL levels. The goal is to "make customizable stem cell products that could be adapted to any particular patient," Ernst says.
Sources: Stem Cell Reports, Science Daily