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Principal Investigator: Daniel C Link
Organization: WASHINGTON UNIVERSITY
Fiscal Year: 2024
Award: $2,109,864
Funding agency: National Cancer Institute
ABSTRACT
The Washington University SPORE in Leukemia is a highly dynamic translational cancer research program that
focuses specifically on leukemias and myelodysplastic syndromes (MDS). We have assembled an outstanding
group of investigators with complementary expertise in basic and clinical leukemia research. In this SPORE, we
leverage expertise in cancer genomics, immunology, and hematopoiesis to develop innovative translational
research in leukemia. Our long-term goal is to develop novel biomarkers and treatments for leukemias and
myelodysplastic syndromes and to develop and promote innovative translational leukemia research. To achieve
these goals, the following specific aims are proposed.
Aim 1. We will exploit institutional expertise in cancer genomics, immunology, and hematopoiesis to
develop novel biomarkers and treatments for leukemias and myelodysplastic syndromes. Basic research
at WUSM has led to the development of the following four translational research projects, three of which feature
innovative investigator-initiated therapeutic trials for leukemias or MDS.
· Project 1. Chimeric antigen receptor T-cell therapy for T cell malignancies
· Project 2. Memory-like NK cell therapy for AML relapsed after allogeneic transplant
· Project 3. Targeted therapy for splicing factor-mutant myeloid malignancies
· Project 4. Targeting ATR in TP53-mutated MDS/AML
Aim 2. We will enhance the infrastructure that supports translational leukemia research. This SPORE
will support the following Shared Research Resources: 1) Core A. Biospecimen Processing; 2) Core B.
Biostatistics and Bioinformatics; and 3) Core C. Administration.
Aim 3. We will recruit and train new investigators in translational research. This SPORE will support a
Career Enhancement Program (CEP) to recruit and mentor new investigators in translational leukemia research,
with an emphasis on under-represented in medicine (URiM) investigators. The SPORE has established a
successful URiM post-baccalaureate training program. The SPORE also will support a Developmental Research
Program (DRP) to support innovative translational concepts.
Aim 4. We will facilitate inter-SPORE collaboration. Two of the SPORE projects include multi-institutional
clinical trials, including participation by peer Leukemia SPORE institutions. We have established a CEP
educational exchange and grant review programs with peer Leukemia SPORE institutions. We will continue to
organize and participate in joint meetings of Leukemia SPOREs at MD Anderson, Harvard, and Memorial Sloan
Kettering Cancer Center.
Terms: <5-Azadeoxycytidine><5-deoxyazacytidine><AML - Acute Myeloid Leukemia><AML/MDS><Acute Lymphoblastic Leukemia><Acute Lymphocytic Leukemia><Acute Lymphoid Leukemia><Acute Myeloblastic Leukemia><Acute Myelocytic Leukemia><Acute Myelogenous Leukemia><Acute T Cell Leukemia><Acute T-Cell Lymphoblastic Leukemia><Acute T-Cell Lymphocytic Leukemia><Acute T-Lymphocytic Leukemia><Allogeneic Transplantation><Allogenic><Antioncogene Protein p53><Basic Research><Basic Science><Bio-Informatics><Bioinformatics><Biometrics><Biometry><Biostatistics><CAR T cell therapy><CAR T cells><CAR T therapy><CAR modified T cells><CAR-T><CAR-Ts><CD7><CD7 gene><Cancer Research Programs><Cancer Research Project><Cancers><Cell Body><Cells><Cellular Tumor Antigen P53><Clinic><Clinical><Collaborations><Communities><Correlative Study><DNA><DNA Replication><DNA Synthesis><DNA biosynthesis><Data><Decitabine><Deoxyazacytidine><Deoxyribonucleic Acid><Development><Dezocitidine><Dysmyelopoietic Syndromes><Early-Stage Clinical Trials><Education><Educational aspects><Female><GP40><Genetic Alteration><Genetic Change><Genetic defect><Genomics><Goals><Grant Review><HSC transplantation><Hematopoiesis><Hematopoietic Cellular Control Mechanisms><Hematopoietic Stem Cell Transplant><Hematopoietic Stem Cell Transplantation><Homologous Transplantation><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Immunology><Infrastructure><Institution><Intention><Investigators><Joints><LEU9><Lytotoxicity><MSKCC><Malignant Neoplasms><Malignant Tumor><Medicine><Memorial Sloan-Kettering Cancer Center><Memory><Mentors><Molecular><Multi-Institutional Clinical Trial><Multi-center clinical trial><Multi-site clinical trial><Multicenter clinical trial><Multisite clinical trial><Mutate><Mutation><Myelodysplastic Disease><Myelodysplastic Syndromes><Myeloid Disease><Myeloid Malignancy><Myeloid Neoplasm><Myeloid Tumor><Myeloproliferative Disorders><Myeloproliferative Tumors><Myeloproliferative disease><NK cell immunotherapy><NK cell therapy><NK cell-based immunotherapy><Natural Killer Cell Immunotherapy><Oncoprotein p53><Oral><P53><PARP Inhibitor><PARP inhibition><PARP-1 inhibitor><PARPi><Patients><Phase 1 Clinical Trials><Phase I Clinical Trials><Phosphoprotein P53><Phosphoprotein pp53><Poly(ADP-ribose) Polymerase Inhibitor><Poly(ADP-ribose) polymerase 1 inhibitor><Postbaccalaureate><Precursor Cell Lymphoblastic Leukemia><Precursor Lymphoblastic Leukemia><Precursor T Lymphoblastic Leukemia><Production><Program Reviews><Protein TP53><R-Series Research Projects><R01 Mechanism><R01 Program><RNA Splicing><Refractory><Refractory Anemia with an Excess of Blasts><Refractory anaemia with excess blasts><Relapse><Research><Research Grants><Research Personnel><Research Project Grants><Research Projects><Research Resources><Researchers><Resolution><Resources><Smoldering Leukemia><Specialized Program of Research Excellence><Splicing><T cells for CAR><T-Cell Type Acute Leukemia><T-Cells><T-Lymphocyte><T-lineage acute lymphoblastic leukemia><TP41><TP53><TP53 gene><TRP53><Testing><Therapeutic Trials><Training><Training Programs><Translating><Translational Research><Translational Science><Tumor Protein p53><Tumor Protein p53 Gene><Universities><Washington><acute granulocytic leukemia><acute lymphatic leukemia><acute lymphogenous leukemia><acute lymphomatic leukemia><acute myeloid leukemia><acute myeloid leukemia/myelodysplastic syndrome><blood cell formation><cancer genomics><career><chimeric antigen T cell receptor><chimeric antigen receptor (CAR) T cell therapy><chimeric antigen receptor (CAR) T cells><chimeric antigen receptor T cell therapy><chimeric antigen receptor T cells><chimeric antigen receptor T therapy><chimeric antigen receptor fusion protein T-cells><chimeric antigen receptor modified T cells><cytotoxicity><developmental><disabled><first in man><first-in-human><genome mutation><hematopoietic cell transplantation><hematopoietic cellular transplantation><hematopoietic progenitor cell transplantation><high risk><inhibitor><innovate><innovation><innovative><leukemia><leukemia relapse><leukemia treatment><leukemic therapy><malignancy><meeting><meetings><mutant><myelodysplasia><myeloproliferative neoplasm><natural killer cell based immunotherapy><natural killer cell therapy><neoplasm/cancer><new approaches><new drug treatments><new drugs><new marker><new pharmacological therapeutic><new therapeutics><new therapy><next generation><next generation therapeutics><novel><novel approaches><novel biomarker><novel drug treatments><novel drugs><novel marker><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel strategies><novel strategy><novel therapeutics><novel therapy><oncogenomics><p53 Antigen><p53 Genes><p53 Tumor Suppressor><peer><phase 2 study><phase I protocol><phase II study><postbac><postbacc><pre-clinical><pre-clinical study><preclinical><preclinical study><programs><protein p53><recruit><replication stress><resolutions><response><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><thymus derived lymphocyte><translation research><translational cancer research><translational investigation><translational investigator><translational researcher><translational scientist>