News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel

News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
Sign In

Cold Spring Harbor Laboratory Researchers Develop Method That Converts Aggressive Cancer Cells into Healthy Cells in Children

If further research confirms these findings, clinical laboratory identification of cancer cells could lead to new treatments for certain childhood cancers

Can cancer cells be changed into normal healthy cells? According to molecular biologists at the Cold Spring Harbor Laboratory (CSHL) in Long Island the answer is, apparently, yes. At least for certain types of cancer. And clinical laboratories and anatomic pathologists may play a key role in identifying these specific cancer cells and then guiding physicians in selecting the most appropriate therapies.

The cancer cells in question are called rhabdomyosarcoma (RMS) and are “particularly aggressive,” according to ScienceAlert. Generally, and most sadly, the cancer primarily affects children below the age of 18. It begins in skeletal muscle, mutates throughout the body, and is often deadly.

“Treatment usually involves chemotherapy, surgery, and radiation procedures. Now, new research by scientists at Cold Spring Harbor Laboratory demonstrates differentiation therapy as a new treatment option for RMS,” Genetic Engineering and Biotechnology News (GEN) reported.

For those young cancer patients, this new research could become a lifesaving therapy as further studies validate the approach, which has been in development for six years.

The CSHL researchers published their findings in the journal Proceedings of the National Academy of Sciences (PNAS) titled, “Myo-Differentiation Reporter Screen Reveals NF-Y as An Activator of PAX3–FOXO1 in Rhabdomyosarcoma.”

Christopher Vakoc, MD, PhD

“Every successful medicine has its origin story,” said Christopher Vakoc, MD, PhD (above), a molecular biologist at Cold Spring Harbor Laboratory, who led the team that develop the method for converting cancer cells into healthy cells. “And research like this is the soil from which new drugs are born.” As these findings are confirmed, it may be that clinical laboratories and anatomic pathologists will be needed to identify the specific cancer cells in patients once treatment is developed. (Photo copyright: Cold Spring Harbor Laboratory.)

Differentiation Therapy

According to an article in the Chinese Journal of Cancer on the National Library of Medicine website, “Differentiation therapy is based on the concept that a neoplasm is a differentiation disorder [aka, differentiation syndrome] or a dedifferentiation disease. In response to the induction of differentiation, tumor cells can revert to normal or nearly normal cells, thereby altering their malignant phenotype and ultimately alleviating the tumor burden or curing the malignant disease without damaging normal cells.”

Vakoc and his team first pursued differentiation therapy to treat Ewing sarcoma, a pediatric cancer that forms in soft tissues or in bone. In January 2023, GEN reported that the researchers had discovered that “Ewing sarcoma could potentially be stopped by developing a drug that blocks the protein known as ETV6.”

“This protein is present in all cells. But when you perturb the protein, most normal cells don’t care,” Vakoc told GEN. “The process by which the sarcoma forms turns this ETV6 molecule—this relatively innocuous, harmless protein that isn’t doing very much—into something that’s now controlling a life-death decision of the tumor cell.”

The researchers discovered that when ETV6 was blocked in lab-grown Ewing sarcoma cells, the cells became normal, healthy cells. “The sarcoma cell reverts back into being a normal cell again,” they told GEN. “The shape of the cell changes. The behavior of the cells changes. A lot of the cells will arrest their growth. It’s really an explosive effect.”

The scientists then turned their attention on Rhabdomyosarcoma to see if they could elicit a similar response.

“In this study, we developed a high-throughput genetic screening method to identify genes that cause rhabdomyosarcoma cells to differentiate into normal muscle. We used this platform to discover the protein NF-Y as an important molecule that contributes to rhabdomyosarcoma biology. CRISPR-based genetic targeting of NF-Y converts rhabdomyosarcoma cells into differentiated muscle, and we reveal the mechanism by which this occurs,” they wrote in PNAS.

“Scientists have successfully induced rhabdomyosarcoma cells to transform into normal, healthy muscle cells. It’s a breakthrough that could see the development of new therapies for the cruel disease, and it could lead to similar breakthroughs for other types of human cancers,” ScienceAlert reported.

“The cells literally turn into muscle,” Vakoc told ScienceAlert. “The tumor loses all cancer attributes. They’re switching from a cell that just wants to make more of itself to cells devoted to contraction. Because all its energy and resources are now devoted to contraction, it can’t go back to this multiplying state,” he added.

Promising New Therapies for Multiple Cancers in Children

Differentiation therapy as a treatment option gained popularity when “scientists noticed that leukemia cells are not fully mature, similar to undifferentiated stem cells that haven’t yet fully developed into a specific cell type. Differentiation therapy forces those cells to continue their development and differentiate into specific mature cell types,” ScienceAlert noted.

Vakoc and his team had previously “effectively reversed the mutation of the cancer cells that emerge in Ewing sarcoma.” It was those promising results from differentiation therapy that inspired the team to push further and attempt success with rhabdomyosarcoma.

Their results are “a key step in the development of differentiation therapy for rhabdomyosarcoma and could accelerate the timeline for which such treatments are expected,” ScienceAlert commented.

Developing New Therapies for Deadly Cancers

Vakoc and his team are considering differentiation therapy’s potential effectiveness for other types of cancer as well. They note that “their technique, now demonstrated on two different types of sarcoma, could be applicable to other sarcomas and cancer types since it gives scientists the tools needed to find how to cause cancer cells to differentiate,” ScienceAlert reported.

“Since many forms of human sarcoma exhibit a defect in cell differentiation, the methodology described here might have broad relevance for the investigation of these tumors,” the researchers wrote in PNAS.

Clinical laboratories and anatomic pathologist play a critical role in identifying many types of cancers. And though any treatment that comes from the Cold Spring Harbor Laboratory research is years away, it illustrates how new insights into the basic dynamics of cancer cells is helping researchers develop effective therapies for attacking those cancers.

—Kristin Althea O’Connor

Related Information:

Aggressive Cancer Cells Transformed into Healthy Cells in Breakthrough

Myo-Differentiation Reporter Screen Reveals NF-Y as An Activator of PAX3–FOXO1 in Rhabdomyosarcoma

Differentiation Therapy: A Promising Strategy for Cancer Treatment

Safer Way to Fight Cancer: Once Rhabdomyosarcoma, Now Muscle

Stopping a Rare Childhood Cancer in Its Tracks

ETV6 Protein Could Be an Important Target for Ewing Sarcoma Treatment

Cancer Cells Turn into Muscle Cells, Potentially Enabling Differentiation Therapy

Novel Ewing Sarcoma Therapeutic Target Uncovered

ETV6 Dependency in Ewing Sarcoma by Antagonism of EWS-FLI1-Mediated Enhancer Activation

Nuclear Transcription Factor Y and Its Roles in Cellular Processes Related to Human Disease

US Army’s Only Deployable Medical Laboratory Highlights Its Mission during Trip to Poland

As a deployable medical laboratory, the 1st AML is designed to run field-based clinical laboratory diagnostics and conduct health threat assessments

Clinical laboratory professionals may be surprised to learn that the US Army has a deployable medical laboratory that is equipped to perform the same menu of basic lab tests as their labs here in the United States, but in support of army units deployed in the field. At the same time, the Army’s deployable medical lab has the added responsibility of testing for infectious diseases and chemicals/agents that could be used by terrorists or enemy forces.

The 1st Area Medical Laboratory (AML) is based out of Aberdeen Proving Ground, Maryland, and operates within the Army’s 20th Chemical, Biological, Radiological, Nuclear and Explosives Command (CBRNE).

“The 1st Area Medical Laboratory identifies and evaluates health hazards through unique medical laboratory analyses and rapid health hazard assessments of nuclear, biological, chemical, endemic disease, occupational, and environmental health threats,” according to an Army new release.

A recent visit by the leaders of this lab unit to meet with their counterparts in Poland highlights the important diagnostic work the military prepares for by using this one-of-a-kind clinical laboratory model.

Col. Matthew Grieser and Col. Przemyslaw Makowski, MD

Col. Matthew Grieser (left), Commander of the 1st Area Medical Laboratory (AML) is shown above meeting with Col. Przemysław Makowski, MD, (right), Deputy Commander of the Military Preventive Medicine Center in Wrocław, Poland. Leaders from the US Army’s 1st AML visited military and medical officials in Poland. “It was a great opportunity to meet our Polish counterparts and to learn from one another,” said Grieser in an Army news release. “We intend to continue to strengthen this relationship … Poland is a great ally, and it was an honor to visit our counterpart organizations.”  (Photo copyright: US Army.)

Role and Makeup of the 1st Area Medical Laboratory

The 1st AML traces its roots back to World War II, where it was one of 19 field laboratories spun up in 1944. It was deactivated after the Vietnam War and then reactivated in 2004. It is currently the Army’s only deployable field laboratory, according to the National Library of Medicine.

This specialized unit deploys worldwide to conduct threat detection and medical surveillance, according to the Army. For example, the military can send the 1st AML to locations where samples cannot quickly be transported to a fixed facility, or where there is a need for immediate hazard identification due to chemical or biological contamination or epidemic disease.

During the Ebola outbreak in Liberia in 2014-2015, the 1st AML operated four blood-testing laboratories and helped oversee two others manned by Navy personnel. The goal was to perform quick turnaround times to identify local residents who carried the disease, all while operating with extensive safety measures. More than 4,500 samples were tested during a six-month stay, Army Times reported.

As Dark Daily covered in “New High-Tech Mobile Medical Laboratories Deployed by the US Navy and a European Consortium Use Genetic Analysis to Get Rapid Diagnosis of Ebola,” one of the Navy labs located at Liberia’s capital, Monrovia, was able to reduce turnaround times for Ebola tests from days to hours.

The unit’s technical expertise features a combination of scientists, clinicians, and certified technicians. Familiar lab personnel include a microbiologist, a biochemist, and medical laboratory technicians.

1st AML Leaders Visit Polish Counterparts

Commanders from the 1st AML recently met with medical officials and chemical, biological, radiological, and nuclear experts from the Polish Armed Forces in the Warsaw area of Poland, the Army news release noted.

During the weeklong trip, 1st AML leaders toured the Epidemiological Response Center of the Polish Armed Forces, Military Institute of Chemistry and Radiometry, laboratories at the Polish Military Institute of Medicine, and biological and chemical labs at the Military Center for Preventive Medicine.

“It was a great opportunity to meet our Polish counterparts and to learn from one another,” said Col. Matthew Grieser, Commander of the 1st AML.

Maj. Suzanne Mate, the Chief of chemical threat assessment for the 1st AML, said meeting with allies helps to keep NATO ready for any contingency.

“It’s better to know your partners before you have to work together in a high-consequence situation,” said Mate in the Army news release. “We learned the strengths in different mobility platforms for laboratories and the capabilities within fixed scientific institutions to maintain standards and currency in chemical, biological, and radiological [CBR] investigations.

“This knowledge is invaluable when determining how to move a sample quickly and efficiently to characterize a suspected CBR threat when airlift resources are constrained or country treaties prevent movement activities,” she added.

Observant clinical laboratory managers will note similarities between their own jobs and those of the 1st AML. The military needs lab-based capabilities to perform a menu of diagnostic tests in support of Army units in the field and traditional clinical laboratories do the same in support of the healthcare providers they service.

Scott Wallask

Related Information:

US Army Field Medical Laboratory Leaders Meet with Polish Counterparts in Warsaw

1st Area Medical Laboratory to Deploy for Ebola Mission

Army Lab Unit Earns Award for Ebola Response in Liberia

New High-Tech Mobile Medical Laboratories Deployed by the U.S. Navy and a European Consortium Use Genetic Analysis to Get Rapid Diagnosis of Ebola

Examining the Utility and Readiness of Mobile and Field Transportable Laboratories for Biodefence and Global Health Security-Related Purposes

California’s Massive Microarray SNP Genotyping Project Processed Genetic Data from More Than 100,000 Volunteers and Characterized 70 Billion Genetic Variants in 14 months

Faster sequencing speed and accuracy could fuel growth of biomarkers and lead to development of new medical laboratory tests and therapeutic drugs

Trailblazing methods used to create a treasure trove of genetic data from 100,000 Californians could pay dividends for clinical laboratories and pathology groups if similar projects identify novel biomarkers and fuel the development of new clinical laboratory tests and therapeutic drugs.

In fact, California is once again in the forefront, this time with a major program to create a big database of genetic data. The program is called the Genetic Epidemiology Research on Adult Health and Aging (GERA). It is a collaboration between the Kaiser Permanente Northern California Research Program on Genes, Environment, and Health (RPGEH) and the Institute for Human Genetics at the University of California, San Francisco (UCSF) that began in 2009. (more…)

‘Genetic Testing Handbook’ Provides Physicians, Pathologists, and Clinical Lab Managers with Comprehensive Reference for Clinical Genome and Exome Sequencing

This new tool offers clinicians the dos and don’ts of genetic testing, what physicians need to know to do it properly 

Clinical use of gene sequencing information has advanced to the point where a team of genetic experts has compiled and issued the Genetic Testing Handbook. The goal of the clinical genome and exome sequencing (CGES) handbook is to provide clinicians—including pathologists and clinical laboratory scientists—with a useful reference tool.

The authors of the Genetic Testing Handbook are Leslie G. Biesecker, M.D., of the National Human Genome Research Institute (NHGRI) in Bethesda, Maryland, and Robert C. Green, M.D., M.P.H., a geneticist who is an Associate Professor of Medicine at Harvard Medical School.

Primer Distills Human Genome Project Technologies for Practical Use

“The technologies that were used for the Human Genome Project are now distilled down to practical tools that clinicians can use to diagnose and, hopefully, treat diseases in patients that they couldn’t treat before,” stated Biesecker, who serves as Chief and Senior Investigator at the NHGRI’s Medical Genomics and Metabolic Genetics Branch, in a press release issued by the National Institutes of Health (NIH). (more…)

;