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MLL Gene May Drive Hematopoietic Stem Cell Production

Apr 21, 2020 10:07:00 AM / by Stacy Matthews Branch, DVM, PhD

Adult and child hands holding orange Ribbons, Leukemia cancer and Multiple sclerosis, COPD and ADHD awareness, world kidney day_AdobeStock_327734588-1Research out of the University of Colorado found that by increasing expression of the MLL gene in induced Pluripotent Stem Cells they could stimulate hematopoietic stem cell production.

The mixed-lineage leukemia 1 (MLL1) gene is disrupted in certain types of acute leukemias due to incorrect fusion with other genes. The majority of patients with leukemias resulting from MLL1 gene fusions are infants under one year of age with primarily acute lymphoblastic leukemias. Some patients with MLL1-related leukemia are those who developed it after treatment with certain chemotherapeutic agents. This subset of patients may rise due to the increased development and use of immunotherapies targeting B-lymphoid cell surface markers.

Researchers at the University of Colorado Cancer Center studied the normal function of MLL1 and its role in leukemia. Hematopoietic stems in MLL1-knockout mice lose stem-cell properties and differentiate to normal blood cells. Once having valuable information regarding what happens when MLL1 expression is prevented, the next step was to determine what could happen if MLL1 expression was instead increased. 

To this end, the researchers developed an MLL1 -inducible embryonic stem cell (ESC) system. Induction of normal (wild-type) MLL1 during the differentiation of ESCs increases hematopoietic stem cell potential. They employed single-cell sequencing experiments to track the differentiation process of the stem cells. The results of the experiments showed that MLL1 induction leads to cells that have properties of multilineage hematopoietic stem cells.

In addition to possibly replenishing hematopoietic stem cells in patients after chemo- or radiotherapy, targeting MLL1 may represent a therapeutic approach to treat MLL1-related childhood leukemia. Conventional chemotherapy and transplantation with hematopoietic stem cells have not led to favorable clinical outcomes. The goal would be to block the leukemia-inducing form of the MLL1 gene while leaving the normal form intact. A precision medicine approach could involve the development of custom stem cell products to treat MLL1-related leukemia. Ongoing studies at the University of Colorado investigate whether disrupting the interaction between MLL and associated cofactors can cause the destruction of leukemia cells.

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Resource:
MLL gene key to producing hematopoietic stem cells, says research. (2020). Drug Target Review. Retrieved 17 March 2020, from https://www.drugtargetreview.com/news/54995/mll-gene-key-to-producing-hematopoietic-stem-cells-says-research/

Topics: Stem Cell Therapy, Stem Cells

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