Juvenile myelomonocytic leukemia or JMML is considered an aggressive type of blood cancer developing in the bone marrow. Usually patients with this form of cancer often display an overproduction of white blood cells. A latest study initiated by the UCSF supposedly floods light on a direct link between an inherited genetic mutation and JMML.
It was ascertained that while inherited genetic mutation is a set of developmental abnormalities, JMML is a rare form of childhood leukemia.
Scientists predict this correlation to have considerable importance in enhancing the diagnosis and treatment of the disease. With the onset of genetic changes, or mutations an abundance of white blood cell production may be observed in genes encoding proteins in the signaling pathway termed as Ras/MAPK pathway. 30 percent of all human cancers are believed to have such mutations in this pathway.
“JMML, like many other pediatric cancers, is essentially development gone awry. By better understanding the developmental biology of cancers in children, we hope to improve our ability to treat them,” explained Mignon Loh, MD, senior author of the study and a pediatric cancer specialist at UCSF Benioff Children’s Hospital.
In accordance to The Leukemia and Lymphoma Society, JMML is generally detected in patients under the age of six and accounts for almost 1.5 percent of all childhood leukemia cases. Claimed to be a curable ailment, scientists confirm only hematopoietic stem cell transplantation (HSCT) to help treat JMML. HSCT is a procedure wherein healthy blood stem cells are extracted from a matched donor and intravenously transplanted into the patient. But even after receiving HSCT condition of approximately 50 percent of patients seems to have deteriorated.
Loh commented, “I think anytime you describe a new developmental syndrome, as we have done here, it enables us to more accurately diagnose children and improve our understanding of how certain proteins, when altered, affect human development and, in this case, contribute to human cancer.”
A prior investigation suggested up to 15 percent of JMML patients develop mutations in a gene known as CBL. In the course of the current study, investigators examined the genetic analysis that revealed the CBL mutation in children with JMML to always appear as a germline event. So it may occur in every cell of the body particularly in the egg or sperm. Probably that is why it is able to pass on from one generation to the next.
A group of 21 children with JMML were scrutinized by the scientists. Having analyzed these patients, experts discovered that along with the consistent germline CBL mutation, a very high percentage of the patients displayed similar developmental abnormalities. Some of the common development abnormalities were overall developmental delay, impaired growth, hearing loss, and a congenital defect termed as cryptorchidism. In this congenital defect, one or both testicles are assumed to have the inability to move into the scrotum before birth.
Charlotte Niemeyer, MD, the study’s first author and a professor of pediatrics at the University of Freiburg in Germany added, “This research moves us significantly closer to understanding what drives JMML and could potentially offer insight into other types of cancer.”
Even the histories of patients’ family and parental DNA were tested by the authors. While scrutinizing it was observed that almost half the families had germline CBL mutations. It can therefore be concluded that through family inheritance or a genetic event in a baby, the CBL mutation found in JMML can arise. By both the ways it can possibly pass on to an affected person’s offspring 50 percent of the time. Investigators will be examining the link between the CBL gene and the development of JMML in the near future. Scientists will probably be demonstrating in cell cultures that the abnormally encoded CBL proteins cause excessive growth of cells, determining that these mutations are cancer causing.
The study is published in the August 8, 2010, Advance Online Publication of the journal Nature Genetics.