Chronic graft-versus-host disease detected by tissue-specific cell-free DNA methylation biomarkers - Prof. Batia Avni
Chronic graft-versus-host disease detected by tissue-specific cell-free DNA methylation biomarkers.
Avni B, Neiman D, Shaked E, Gal-Rosenberg O, Grisariu S, Kuzli M, Avni I, Fracchia A, Stepensky P, Zuckerman T, Lev-Sagie A, Fox-Fisher I, Piyanzin S, Moss J, Salpeter SJ, Glaser B, Shemer R, Dor Y. J Clin Invest. 2024 Jan 16; 134(2):e163541. doi: 10.1172/JCI163541.PMID: 37971879
Tissue specific cell free DNA methylation markers for detection and tracking of chronic Graft Versus Host Disease.
Hematopoietic cell transplantation (HSCT) is a crucial and often the sole curative treatment strategy for relapsed and refractory hematologic malignancies. Graft versus host disease (GVHD), the foremost complication of allogeneic HSCT, significantly impacts patients' quality of life and increases mortality associated with the procedure. The current diagnostic methods for GVHD in bone marrow transplant patients rely on imprecise phenotypic markers and occasionally involve biopsies. These approaches result in inaccurate, costly, and invasive diagnoses, often at later stages of the disease, negatively impacting patients' health and survival and leading to non-specific treatments.
Accurate biomarkers for predicting disease occurrence, identifying disease onset, gauging response to treatment, and assessing treatment efficacy are notably absent. Tissue-specific DNA methylation patterns are robust, universally applicable biomarkers. These patterns can identify the tissue origin of cell-free DNA (cfDNA), reflecting increased turnover or damage in specific organs, regardless of the underlying pathology.
Recently, Prof. Avni B. in collaboration with Prof. Dor Y. and Prof. Shemer Ruth from the Hebrew University-Faculty of Medicine have shown that tissue-specific DNA methylation patterns can serve as plasma biomarkers for detecting tissue turnover in chronic GVHD. This research has revealed a general increase in cfDNA concentration in cGVHD patients, along with elevated cfDNA originating from specific organs, immune cells, and inflammatory cells. By combining cfDNA markers with conventional biochemical markers, they have been able to effectively differentiate between patients with and without cGVHD, achieving good sensitivity, accuracy, and precision.
Together with Dr Sigal Grisariu from the BMT department at Hadassah, Prof. Ruth Shemer from the Hebrew university-Faculty of Medicine and Dr. Dana Yehudai-Ofir from Rambam center, Prof. Avni was granted the ISF MAVRI program grant to develop multiplex PCR cocktails. These cocktails will be used to measure the proportion of unmethylated DNA molecules in serial patient samples collected before and after HSCT, as well as from healthy individuals. Once a cGVHD detection algorithm is established, the team will focus on developing a cfDNA-based algorithm to evaluate treatment response in patients with cGVHD.
Published manuscripts