PROJECT SUMMARY/ABSTRACT Juvenile myelomonocytic leukemia (JMML) is a rare, fatal childhood disease that affects infants and young children less than 4 years of age. JMML is characterized by aberrant myeloid cell overproduction and hypersensitivity to GM-CSF. The only curative therapy is allogeneic hematopoietic stem cell transplantation; however, approximately half of children relapse after this aggressive therapy. Over several years, an international community of families, scientists, and clinicians have merged their efforts to advance the research and improved treatment for JMML. A key unifying aspect of this collaborative effort has been the bi-annual International JMML Symposia alternating with bi-annual JMML Working Groups which precede the annual American Society of Hematology (ASH) meetings. These pre-ASH meetings (supported by the NCI via this R13 conference grant since 2007) provide the perfect locale for gathering of JMML clinicians and scientists from Europe, Japan, and the United States, and afford an efficient means of stimulating open communication and collaboration between the various groups. After our most current meeting (December 4, 2015 in Orlando, FL), participants of the 2015 JMML Working Group updated the ?JMML Roadmap? and identified three main areas that need to be addressed and refined based on emerging basic and clinical research findings in the area of JMML: 1) Functional evaluation of secondary mutations found to co-exist with RAS pathway mutations in JMML patients; 2) Integration of diagnostic evaluation for children presenting with JMML and RAS-associated lymphoproliferative disorder (RALD); 3) Development of international database to enhance pre-transplant diagnosis and treatment based on genomic mutations and to optimize post-transplant immunosuppression regimens. To maintain the momentum of this international group of researchers and to carry forward these goals, we seek support for the 2016 JMML International Symposium, which will be held in conjunction with the American Society of Hematology annual meeting in San Diego, CA. The PI for this meeting, Rebecca J. Chan, M.D., Ph.D., is a member of the JMML Foundation Board of Directors and researcher in the field. Additionally, Mignon L. Loh, M.D., a JMML researcher and clinician, Mr. Fred Dini, President of the JMML Foundation, and Ms. Kelli Barnes, member of the JMML Foundation Board of Directors, will also be part of the conference planning team.