UC San Diego School of Medicine and Moore’s Cancer Center have established the identity of RNA-based biomarkers that differentiate between regular (normal) aging hematopoietic stem cells and leukemia stem cells linked to secondary acute myeloid leukemia of sMAL, a difficult form of leukemia occurring in older individuals many times after they have already experienced cancer.
To review, hematopoietic stem cells (HSCs), or hemocytoblasts, are the stem cells associated with the blood. Developing in mesoderm in bone marrow, hematopoietic stem cells in a process called hematopoiesis spawn all other forms of blood cells.
The findings, published in Cell Stem Cells, indicate ways to identify the possibility of a relapse of leukemia much earlier and information that could lead to the development of new drugs.
Secondary acute myeloid leukemia tends to be a disease associated with individuals over 60. Rates of survival are low for these individuals, and the elderly are not ideally suited for such rigorous procedures such as bone marrow transplants. Thus, age – advanced age – is a huge consideration in determining the risk factor for secondary acute myeloid leukemia.
As we age, hematopoietic stem cells (the good cells) suffer DNA mutations that trigger DNA instructions like RNA and proteins. This makes telling the difference between aging hematopoietic stem cells and secondary acute myeloid leukemia difficult.
The study focused on RNA changes coinciding with the aging of normal blood stem cells in comparison to leukemia stem cells. Gene sequencing technology was used to pick out particular RNA-splicing variants that show the difference between normal blood stem cells that are aging and leukemia stem cells. They separated the two via characteristic RNA splicing patterns; thus being able to target treatment regimens based upon identifying leukemia stem cells and avoiding normal blood stem cells.
One item of note is RNA-splicing targets are active in a wide cross-section of “solid” tumors; so there are treatment implications for solid tumor cancer particularly ones that are resistant to currently available drug regimens.