In biomedical research, cell lines allow scientists to study human biology and disease in a controlled setting. Among thousands of available cell lines, the HL-60 line holds a distinct position. It is a continuously dividing line of human cells used to study blood cell development, cancer biology, and drug action. Its properties have made it a staple in laboratories worldwide, contributing to advances in basic science and clinical medicine.
Origin and Nature of the HL-60 Cell Line
The HL-60 cell line is an immortalized line, which means its cells can proliferate indefinitely under laboratory conditions, providing a consistent and renewable resource for experimentation. This cell line was established in 1977 from the peripheral blood cells of a patient with acute promyelocytic leukemia (APL). It was the first human myeloid leukemia cell line that could be grown continuously in suspension.
These cells are promyelocytes, an early, immature stage in the development of a white blood cell known as a granulocyte. They grow as suspension cells, floating freely in the liquid culture medium, which simplifies their maintenance. Genetically, the HL-60 cell line is aneuploid, containing an abnormal number of chromosomes, a common feature of cancer cells.
The Hallmark Trait of Differentiation
A defining characteristic of HL-60 cells is their capacity for differentiation, the process by which a less specialized cell becomes a more specialized cell type. While derived from a leukemia that traps them in an immature state, they can mature into various white blood cells when prompted by chemical signals in the lab. This malleability makes them a valuable research tool.
Scientists can manipulate the developmental fate of HL-60 cells by adding different inducing agents to their culture medium. For instance, compounds like dimethyl sulfoxide (DMSO) or all-trans retinoic acid (ATRA) can trigger the cells to differentiate into cells that resemble mature neutrophils. This process involves genetic changes, including the downregulation of the c-Myc gene, which is associated with proliferation.
By using other agents, such as vitamin D3 or phorbol esters like PMA, researchers can guide HL-60 cells to mature into monocytes and macrophages. This ability to generate different, functional immune cell types from a single source allows scientists to study the processes of blood cell development and the specific functions of these mature cells in a controlled environment.
Applications in Scientific Research
The ability of HL-60 cells to differentiate has led to their widespread use. One area is the study of apoptosis, or programmed cell death, a process often dysregulated in cancer. Researchers use HL-60 cells to investigate how compounds can trigger or inhibit this mechanism, providing insights into potential cancer therapies.
These cells are also a staple in toxicology and drug screening. They provide a model to assess how new chemical compounds affect human-like cells by measuring outcomes like cell viability and proliferation. This helps identify potentially harmful effects early in the drug development pipeline.
Because they can be differentiated into neutrophil-like cells, they serve as a model for studying immune function. Researchers use differentiated HL-60 cells to investigate processes like chemotaxis, where cells migrate toward a chemical signal, and phagocytosis, where cells engulf pathogens.
Modeling Disease and Therapeutic Response
Beyond general applications, HL-60 cells provide a specific model for the disease from which they were derived: acute promyelocytic leukemia (APL). Because the cells originate from an APL patient, they mirror aspects of the disease at a cellular level, allowing researchers to study its pathology. This relevance led to the development of a new treatment for APL.
Experiments showed that all-trans retinoic acid (ATRA) could force HL-60 cells to overcome their developmental block and differentiate into mature granulocytes. This finding suggested that instead of killing the cancerous cells, it might be possible to treat the disease by simply making the cells mature. This concept, known as differentiation therapy, was a departure from conventional cancer treatment.
This laboratory observation was translated directly into the clinic. When APL patients were treated with high doses of ATRA, their leukemic promyelocytes matured, and many achieved complete remission. The success of ATRA transformed APL from a highly fatal disease into one that is now highly curable, illustrating how research on a cell line can lead to a clinical therapy.