Researchers at the University of Colorado Cancer Center have identified a new way to coax pluripotent stem cells (iPSCs) into making hematopoietic stem cells (HSCs) by magnifying the MLL gene, a gene that can cause a form of childhood leukemia, according to a study published in Stem Cell Reports.

Current research has centered around the ability to make personalized blood stem cells to treat patients with leukemia. In the past, researchers have sampled adult cells with the goal of deprograming them in order to create induced iPSCs capable of forming any of the body’s cell types, including blood cells. However, these iPSCs also have the potential of becoming cancer.

In response, researchers have begun to make hematopoietic stem cells (HSCs). Although they cannot make any cell type like iPSCs, they can produce many types of blood cells and do not have risk of cancer like iPSCs, according to the study authors.

Researchers examined the MLL fusion gene in hopes of discovering how to stop its ability to cause cancer. When they “knocked out” the gene, the researchers found these HSCs would differentiate to become like normal blood cells instead of remaining HSCs, according to the study’s press release.

In doubling the amount of the regular MLL protein in iPSCs, researchers found that these cells produced more normal blood cells. The study authors believe that this finding may help to develop usable HSCs that could regrow a patient with leukemia’s blood system after chemotherapy and irradiation.

The findings also have important ramifications for ongoing drug development against MLL-rearranged childhood leukemia, namely that drugs affecting the healthy MLL gene, along with the rearranged form of the MLL gene, may have negative consequences for blood functions, according to the authors.

The purpose of the study was to selectively target the cancer-causing MLL fusion gene without affecting the MLL gene’s regular form. Researchers found that as iPSCs differentiate, they enter a transitional state in which they have the potential to become different cell types. Through single-cell sequencing, the study authors found that activating MLL led to these transitional cells becoming blood cell types.

Genetic engineering could allow researchers to activate MLL in a population of pluripotent cells by adding additional copies of the MLL gene to the pluripotent cells’ genome. That approach is not seen as practical in human patients. Instead, researchers plan to pursue the development of a drug-based method to amplify the level of existing MLL.

Reference
Sundem, Garth. Cancer study may accidentally help researchers create usable blood stem cells. University of Colorado Cancer Center website. Published January 16, 2020. https://coloradocancerblogs.org/mll-blood-stem-cells/. Accessed January 29, 2020.