Researchers at the Jackson Laboratory (JAX) in the United States have developed a new method to determine the cell type that causes a given type of leukemia by performing a whole-genome analysis of open chromatin. This method plays an important role in the diagnosis and treatment of leukemia.
Every cancer starts with a single cell mutation. Knowing the cell of origin of cancer cells, researchers can analyze the subtype of the cancer and develop new diagnosis and treatment methods. However, it is difficult for existing methods to identify the cells of origin from a large number of tumor cell samples.
Chromatin is an important component in the cell nucleus. It is composed of DNA, histones, and RNA. It condenses into chromosomes during a specific stage of cell division. Each type of cell has a unique chromatin structure. Closed chromatin will be tightly wrapped around the nucleosome and is relatively inactive; the connection between open chromatin and nucleosome is relatively loose and more active. Dr. Jennifer Trowbridge, an assistant professor in the Jackson Laboratory, has improved the current method of identifying the origin of tumor cells by analyzing the open chromatin in tumor cells.
Trowbridge led his laboratory colleagues to construct a mouse model of acute myeloid leukemia (AML). They identified five types of cells from the bone marrow of humans and mice: long-term hematopoietic stem cells, short-term hematopoietic stem cells, pluripotent progenitor cells, common myeloid progenitor cells, and granulocyte macrophage progenitor cells. AML caused by these cells of different origins shows different invasiveness in mice: the lesions caused by stem cells are more invasive, while the lesions caused by progenitor cells are much less invasive. The frequency of leukemia cells induced by different invasiveness is also different: stem cells are high, progenitor cells are low.
Researchers analyzed the open chromatin of different AML cell samples and compared them with the open chromatin patterns in normal cells to determine the characteristics and gene expression patterns of open chromatin in AML cell samples, which allowed them to extract stem cells. Initiated AML is distinguished from AML caused by progenitor cells.
The researchers said that by further studying the open chromatin of stem and progenitor cells in healthy people and AML patient populations, they can determine more precise cancer biomarkers based on cell origin, which is of great significance for cancer diagnosis and treatment .