We propose to create an integrated Leukemia Translational Science Center (LTSC), which will generate, coordinate and lead translational studies in leukemia within ECOG-ACRIN and within the National Clinical Trials Network (NCTN). The LTSC will serve as the central hub for studies of the Leukemia Laboratory Committee (LLC), with the support of the Leukemia Translational Laboratory (LTRL), the Leukemia Tissue Bank (LTB), and a comprehensive Leukemia Data Warehouse. The LTSC is led by E. Paietta, A. Melnick and R. Levine, who collectively lead the LLC, LTRL and LTB. Through these initiatives, they have developed an extensive track record in translational research leadership and implementation of state-of-the-art correlative studies in leukemia biology. The LTSC is further enhanced through its partnership with the New York Genome Center, which provides access to high-throughput genomics technologies, state-of-the-art genomic platforms, computational resources, and the capability to perform extensive, CLIA-certified, clinical genomics assays. In order to maximally accelerate high quality clinical trials based on the most important science, the LTSC will establish an interaction framework that will attract junior and senior clinical investigators, laboratory scientists, computational biologists, biostatisticians and others, and enable them to form synergistic research teams. The LTSC will provide pilot project funding for cross-disciplinary teams to jump-start these projects and an extensive suite of scientific resources, including patient specimens, the LTRL, access to the New York Genome Center, genomic and epigenetic profiling databases, and scientific support. In this way, the LTSC will ensure that translational scientific studies are seamlessly integrated into leukemia clinical trials to identify predictors of response/outcome, identify and test novel therapies, and develop innovative correlative studies to assess response to anti-leukemia therapies. Through these activities, the LTSC expects to transform the standard practice of leukemia care with the development and implementation of personalized diagnostic methods, biomarkers and therapies.
Advances in the treatment of hematologic disorders have been disappointing. The ECOG-ACRIN Leukemia Translational Science Center will create, support, and synergize partnerships between clinical and laboratory investigators and foster the continuous, near-term translation of state-of-the art laboratory studies into clinical trials to improve outcomes for leukemia patients.
|Perez-Andreu, Virginia; Roberts, Kathryn G; Xu, Heng et al. (2015) A genome-wide association study of susceptibility to acute lymphoblastic leukemia in adolescents and young adults. Blood 125:680-6|
|Kharabi Masouleh, Behzad; Geng, Huimin; Hurtz, Christian et al. (2014) Mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 111:E2219-28|
|Li, Sheng; ?abaj, Pawe? P; Zumbo, Paul et al. (2014) Detecting and correcting systematic variation in large-scale RNA sequencing data. Nat Biotechnol 32:888-95|
|SEQC/MAQC-III Consortium (2014) A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium. Nat Biotechnol 32:903-14|
|Rampal, Raajit; Alkalin, Altuna; Madzo, Jozef et al. (2014) DNA hydroxymethylation profiling reveals that WT1 mutations result in loss of TET2 function in acute myeloid leukemia. Cell Rep 9:1841-55|
|Roberts, Kathryn G; Li, Yongjin; Payne-Turner, Debbie et al. (2014) Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med 371:1005-15|
|Ntziachristos, Panagiotis; Tsirigos, Aristotelis; Welstead, G Grant et al. (2014) Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia. Nature 514:513-7|