“Together, we've found a novel mutation in a cell signaling pathway, that's not mutated in any other form of cancer, said Charles Mullighan, MD, MBBS, St. Jude Pathology.
Cancer has many different causes. One common feature is uncontrolled cell growth. Scientists at St. Jude and the Munich Leukemia Laboratory found a new cause of the uncontrolled growth of natural killer (NK) cells. NK cells are a type of immune cell that normally kills infected or tumor cells.
The team looked at a poorly understood form of chronic leukemia. The leukemia is chronic lymphoproliferative disorder of natural killer cells (CLPD-NK). In this disease, NK cells become cancerous. But scientists did not know how that happens.
The researchers showed that a mutated gene called CCL22 attracts immune cells more potently than normal CCL22. These immune cells then signal NK cells to multiply, resulting in cancer.
The results led the scientists to create a new model of cancer development.
“Together, we've found a novel mutation in a cell signaling pathway, that's not mutated in any other form of cancer, said Charles Mullighan, MD, MBBS, Pathology.
"When we found the first mutations in CCL22 in our whole genome sequencing data set we felt that this could be the beginning of a new chapter for CLPD-NK patients,” said co-corresponding author Torsten Haferlach, MD, PhD, of Munich Leukemia Laboratory. “This never would have been possible without such outstanding and multidisciplinary team of dedicated scientists at St Jude."
The scientists hope this work will serve as a proof-of-principle for how other cancers may form.
Nature Genetics published this work.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food — because all a family should worry about is helping their child live. To learn more, visit stjude.org or follow St. Jude on social media at @stjuderesearch.