CDI Laboratory Explores Pathway to Open up Blood Cancer Treatments

The paper in Nature Communications could mean better treatment for leukemia, among other cancers

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Feb 12, 2020, 16:47 ET

NUTLEY, N.J., Feb. 12, 2020 /PRNewswire/ -- Reversing runaway inflammation in the bone marrow could lead to major breakthroughs in treatments for some blood cancers, according to a new publication by scientists at Hackensack Meridian Health's Center for Discovery and Innovation (CDI).

The CDI team's findings could ultimately improve cancer treatments for people of advanced age, like that of adult acute myeloid leukemia (AML), as they indicate in the paper in the journal Nature Communications.

Center for Discovery and Innovation (PRNewsfoto/Hackensack Meridian Health)

The study, published Feb. 3, demonstrates how endothelial (blood vessel lining) cells orchestrate inflammatory stress within the microenvironment of the bone marrow.

The scientists demonstrated the function of two connected pathways involved in myelosuppressive injuries (like those caused by chemotherapy), in which bone marrow activity decreases, leading to less blood cell production.

The myelosuppression leads to chronic activation of the mitogen-activated protein kinase (MAPK) pathway – causing local and systemic inflammation, in turn driven by the Nuclear factor-kB (NF-kB) signaling pathway. This chronic inflammation resulted in disruption of the integrity of blood vessels and functional defects to the hematopoietic stem cell.

Utilizing a genetic model to block the NF-kB dependent endothelial inflammation, led to the discovery of a novel protein, Stem Cell Growth Factor Alpha (SCGFa).

The SCGFa was tested, and the models' data showed promise. The SCGFa preserved vascular function and promoted hematopoietic recovery and hematopoietic stem cell function when infused following myelosuppressive treatments, such as chemotherapy. The scientists were also able to tamp down the vascular and hematopoietic inflammation by the administration of SCGFa, which boosted the recovery following the inflammation.

"We showed that SCGFa could be used therapeutically, to allow recovery of these crucial systems following myelosuppression," said Pradeep Ramalingam, the study's lead author.

"The elderly population tend to do worse following cancer treatments that result in myelosuppressive injury, since their bodies can't sustain as much chemotherapy as the young can," said Jason Butler, Ph.D., an associate member of the CDI, and the senior author, whose work is also part of the Georgetown Lombardi Comprehensive Cancer Center's National Cancer Institute-designated consortium. "But if we infuse patients with SCGFa, we may be able to protect their hematopoietic system and allow for rapid regeneration and rejuvenation of their bone marrow. This would allow us to potentially give patients more chemotherapy – and ultimately lead to better outcomes and lower relapse rates."

Dr. Butler and his laboratory are currently working on exciting future directions for the work, including the direct effects of SCGFa on hematopoietic stem cells – and how SCGFa may enhance the homing, engraftment, and function of hematopoietic stem cells following bone marrow transplants.

"These studies will become important to understand the precise molecular mechanisms by which SCGFa enhances hematopoietic regeneration and to develop treatment strategies directed towards protecting the hematopoietic system and the (bone marrow) endothelial niche following myelosuppressive therapies," the authors concluded.

ABOUT HACKENSACK MERIDIAN HEALTH

Hackensack Meridian Health is a leading not-for-profit health care organization that is the largest, most comprehensive and truly integrated health care network in New Jersey, offering a complete range of medical services, innovative research and life-enhancing care.

Hackensack Meridian Health comprises 17 hospitals from Bergen to Ocean counties, which includes three academic medical centers – Hackensack University Medical Center in Hackensack, Jersey Shore University Medical Center in Neptune, JFK Medical Center in Edison; two children's hospitals - Joseph M. Sanzari Children's Hospital in Hackensack, K. Hovnanian Children's Hospital in Neptune; nine community hospitals – Bayshore Medical Center in Holmdel, Mountainside Medical Center in Montclair, Ocean Medical Center in Brick, Palisades Medical Center in North Bergen, Pascack Valley Medical Center in Westwood, Raritan Bay Medical Center in Old Bridge, Raritan Bay Medical Center in Perth Amboy, Riverview Medical Center in Red Bank, and Southern Ocean Medical Center in Manahawkin; a behavioral health hospital – Carrier Clinic in Belle Mead; and two rehabilitation hospitals - JFK Johnson Rehabilitation Institute in Edison and Shore Rehabilitation Institute in Brick.

Additionally, the network has more than 500 patient care locations throughout the state which include ambulatory care centers, surgery centers, home health services, long-term care and assisted living communities, ambulance services, lifesaving air medical transportation, fitness and wellness centers, rehabilitation centers, urgent care centers and physician practice locations. Hackensack Meridian Health has more than 34,100 team members, and 6,500 physicians and is a distinguished leader in health care philanthropy, committed to the health and well-being of the communities it serves.

The network's notable distinctions include having four hospitals among the top 10 in New Jersey by U.S. News and World Report. Other honors include consistently achieving Magnet® recognition for nursing excellence from the American Nurses Credentialing Center and being named to Becker's Healthcare's "150 Top Places to Work in Healthcare/2019" list.

The Hackensack Meridian School of Medicine at Seton Hall University, the first private medical school in New Jersey in more than 50 years, welcomed its first class of students in 2018 to its On3 campus in Nutley and Clifton. Additionally, the network partnered with Memorial Sloan Kettering Cancer Center to find more cures for cancer faster while ensuring that patients have access to the highest quality, most individualized cancer care when and where they need it.

Hackensack Meridian Health is a member of AllSpire Health Partners, an interstate consortium of leading health systems, to focus on the sharing of best practices in clinical care and achieving efficiencies.

For additional information, please visit www.HackensackMeridianHealth.org.

About the Center for Discovery and Innovation

The Center for Discovery and Innovation, a newly established member of Hackensack Meridian Health, seeks to translate current innovations in science to improve clinical outcomes for patients with cancer, infectious diseases and other life-threatening and disabling conditions. The CDI, housed in a fully renovated state-of-the-art facility, offers world-class researchers a support infrastructure and culture of discovery that promotes science innovation and rapid translation to the clinic.

About John Theurer Cancer Center at Hackensack University Medical Center

John Theurer Cancer Center at Hackensack University Medical Center is New Jersey's largest and most comprehensive center dedicated to the diagnosis, treatment, management, research, screenings, and preventive care as well as survivorship of patients with all types of cancers. The 14 specialized divisions covering the complete spectrum of cancer care have developed a close-knit team of medical, research, nursing, and support staff with specialized expertise that translates into more advanced, focused care for all patients. Each year, more people in the New Jersey/New York metropolitan area turn to John Theurer Cancer Center for cancer care than to any other facility in New Jersey. John Theurer Cancer Center is a member of the Georgetown Lombardi Comprehensive Cancer Center Consortium, one of just 16 NCI-approved cancer research consortia based at the nation's most prestigious institutions. Housed within a 775-bed not-for-profit teaching, tertiary care, and research hospital, John Theurer Cancer Center provides state-of-the-art technological advances, compassionate care, research innovations, medical expertise, and a full range of aftercare services that distinguish John Theurer Cancer Center from other facilities. For additional information, please visit www.jtcancercenter.org.

SOURCE Hackensack Meridian Health