MAY 21, 2014
Research on Langerhans Cell Histiocytosis leads to diagnostic test and potential new therapies.
Doctors propose classification of LCH as a myeloid neoplasia.
Your generous donations helped fund a remarkable breakthrough project that was just recently published in the Journal of Experimental Medicine. Co-authored by Drs. Kenneth McClain, Carl Allen and Stephen Simko from Texas Children’s Cancer Center, the study defines clinically distinct LCH risk groups, identifies the cell of origin of LCH, and proves that BRAF-V600E expression drives a LCH-like condition in a mouse model.
The research uncovers important fundamental understanding of Langerhans Cell Histiocytosis. Perhaps more importantly to patients and parents, the research advances development of new diagnostic tests and is likely to inform new treatment therapies.
What did researchers/doctors learn?
Researchers used lesion biopsies from 100 LCH patients collected/stored at Texas Children’s Hospital over the last 10 years. The LCH lesion biopsies were paired with patient blood samples and analyzed. The study finds that a mutation in BRAF gene, BRAF-V600E, was specifically identified in the blood and bone marrow of high-risk LCH patients, but not in circulating blood cells of low-risk LCH patients.
“LCH is a mysterious disease, and the causes have not been very well characterized,” said Dr. Carl Allen, Assistant Professor of Pediatrics at Baylor and Texas Children’s Cancer Center. “Observations from this study may help explain why some patients develop a single lesion or limited disease while others may develop disseminated life-threatening disease. Our hope is that these findings may lead to improved personalized diagnostic and therapeutic strategies for patients with LCH.”
What does this mean?
The study shows that high-risk LCH is determined by a BRAF mutation of precursor cells that develop into myeloid dendritic cells which then migrate to other organs and form tumors. This clinically defines LCH as a myeloid neoplasm, which is the cancer family of diseases. This is huge news for those affected by Histiocytosis. Currently, little to no government funding is provided for research because Histiocytosis is considered an “orphan” disease. But, if Histiocytosis can officially be labeled as a cancer, then that opens new doors for funding and support that were previously unavailable.
Why is this so important?
Based upon the results of this study, Drs. McClain, Allen and Simko, and their incredible team are developing diagnostic blood testing methods for LCH to determine clinical risk factors and to follow treatment results. Furthermore, the study provides a better understanding of BRAF mutated cells and helps optimize treatment therapies to target early myeloid dendritic cells and prohibit the maturation of LCH precursor cells.
The Histio CURE Foundation proudly funded and supported this research by committing your generous donations ($700,000 between 2011 and 2013) to finding a cure. The support from HCF is acknowledged in the published journal article. Our continued ability to support such ground breaking research is because of our gracious donors. Thank you all!
Presently, the study is available in the April issue of the Journal of Experimental Medicine. You can view the abstract HERE. The full study is currently available for purchase but please check back here as The Histio CURE Foundation intends to make this paper available on our website when licensing allows.
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|2011-1: Dec 2011 $150K ($147K Dec 2011, $3K April 2012)
Kenneth L. McClain, M.D., Ph.D. - Director of Histiocytosis Program
Carl E. Allen, M.D., Ph.D. - Director of Histocytosis Research Laboratory
“Spit for a Cure” – Defining Inherited Risk Factors in Histiocytic Disorders.
The blood stem cell matures through different pathways to produce many different types of histiocytes, now called dendritic cells (DC), that are central to the pathology of the histiocytic diseases. Langerhans cell histiocytosis (LCH), Juvenile Xanthogranuloma (JXG), Erdheim Chester Disease (ECD), Hemophagocytic Lymphohistiocytosis (HLH), and Rosai Dorfman Disease (RD) are all thought to result from abnormal dendritic cell development and function. The question remains, what genes or pathways malfunction and are responsible for these diseases?
While the scope and potential impact of this project is global, the design is relatively simple. With new genomic technology, we can obtain an incredible amount of genetic information just from a spit sample. By analyzing and comparing the genetic information of a patient and the parents from several hundred families, we hope to identify and uncover the inherited risk factors in all Histiocytic Diseases.
Our goal for the first phase of this global study is to enroll 500 triads (patients and parents). All patients with a histiocytic disorder and parents are welcome to participate in this study. Please visit our Spit for a Cure webpage for more information.