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Principal Investigator: Lachelle Dawn Weeks
Organization: DANA-FARBER CANCER INST
Fiscal Year: 2024
Award: $165,080
Funding agency: National Heart Lung and Blood Institute
Project Summary
Clonal hematopoiesis (CH) is the pre-malignant expansion of a population of blood cells derived from a single
hematopoietic stem cell and is often caused by somatic mutations in leukemia driver genes. CH has been
associated with significant clinical outcomes including hematologic cancers, various inflammatory
comorbidities, and increased all-cause mortality. Among individuals with CH, there is inconsistent penetrance
for inflammatory disease symptoms and risk of inflammatory disease varies widely. Reliable clinically-validated
models that estimate a patient’s risk of inflammatory disease outcomes and management strategies that
prevent or effectively overcome inflammatory disease outcomes in CH are major medical needs. The goal of
this proposal is to define and better understand the relationship between CH and inflammatory disease
outcomes. Aim 1 will define the association between CH and rheumatologic diseases and activities in Aim 2
will define the CH genotypes most powerfully linked to inflammatory phenotypes and generate a statistical
algorithm to estimate individual risk of inflammatory disease in patients with CH. Then, using a cohort of
patients with clonal cytopenia of uncertain significant (CCUS), a subtype of CH, who have been exposed to
hypomethylating agents (HMA), Aim 3 will explore the influence of HMA therapy on inflammatory disease
symptoms. Collectively, this work will enable the identification of patients with CH who are at risk for
inflammatory diseases and provide preliminary data to motivate future interventional clinical trials with
endpoints designed around prevention of inflammatory disease outcomes. Dr. Lachelle D. Weeks is a
hematologist and scientist at the Dana-Farber Cancer Institute (DFCI) and translational investigator in the
Division of Population Sciences within the Department of Medical Oncology at DFCI. She spends 80% of her
time in translational research and 20% in clinical practice caring for and counseling patients with CH and
myelodysplastic syndrome (MDS). In addition to her primary mentor, Dr. Weeks has established an advisory
committee of internationally recognized experts in CH, myeloid malignancies, clinical computational oncology,
and genetic epidemiology. Her research and career development activities will be conducted at DFCI which
has an outstanding research community and a long track record for successful mentorship of independent
scientists. This is an ideal environment for completion of the proposed research, execution of the proposed
career development strategy, and the ultimate realization of Dr. Weeks’s long-term career goal of becoming an
R01-funded physician-scientist.
Terms: <AML - Acute Myeloid Leukemia><Acute Myeloblastic Leukemia><Acute Myelocytic Leukemia><Acute Myelogenous Leukemia><Advisory Committees><Algorithms><Arthritis><Biology><Blood><Blood Cells><Blood Precursor Cell><Blood Reticuloendothelial System><Cancers><Caring><Case-Base Studies><Case-Comparison Studies><Case-Compeer Studies><Case-Referent Studies><Case-Referrent Studies><Case/Control Studies><Cell Body><Cells><Chronic><Chronic Myelomonocytic Leukemia><Clinical><Clinical Data><Clinical Research Protocols><Clinical Trials><Communities><Counseling><Cranial Arteritis><DF/HCC><Dana-Farber Cancer Institute><Data><Data Banks><Data Bases><Data Set><Databanks><Databases><Dedications><Development><Development and Research><Diagnosis><Disease><Disease Management><Disease Outcome><Disorder><Disorder Management><Dose><Dysmyelopoietic Syndromes><Electronic Health Record><Environment><Excess Mortality><Exposure to><Funding><Future><Genes><Genetic><Genetic Alteration><Genetic Change><Genetic defect><Genomics><Genotype><Giant Cell Arteritis><Goals><Gout><HSC expansion><Health Insurance for Aged and Disabled, Title 18><Health Insurance for Disabled Title 18><Hematologic Cancer><Hematologic Malignancies><Hematologic Neoplasms><Hematological Malignancies><Hematological Neoplasms><Hematological Tumor><Hematologist><Hematopoiesis><Hematopoietic Cancer><Hematopoietic Cell Tumor><Hematopoietic Cellular Control Mechanisms><Hematopoietic Malignancies><Hematopoietic Neoplasms><Hematopoietic Neoplasms including Lymphomas><Hematopoietic Progenitor Cells><Hematopoietic Tumor><Hematopoietic and Lymphoid Cell Neoplasm><Hematopoietic and Lymphoid Neoplasms><Hematopoietic stem cells><Horton Disease><Horton Giant Cell Arteritis><Horton's Giant Cell Aortitis><Immune><Immune memory><Immune signaling><Immunes><Immunologic Memory><Immunological Memory><Individual><Inflammation><Inflammatory><International><Intervention><Intervention Strategies><Label><Laboratories><Link><Malignant><Malignant - descriptor><Malignant Hematologic Neoplasm><Malignant Hematopoietic Neoplasm><Malignant Neoplasms><Malignant Tumor><Medical><Medical Oncology><Medicare><Mentors><Mentorship><Modeling><Molecular><Morbidity><Morbidity - disease rate><Musculoskeletal Pain Disorder><Mutate><Mutation><Myelodysplastic Disease><Myelodysplastic Syndromes><Myeloid Disease><Myeloid Malignancy><Myeloid Neoplasm><Myeloid Tumor><Myeloproliferative Disorders><Myeloproliferative Tumors><Myeloproliferative disease><Non-Malignant><Oncology><Oncology Cancer><Outcome><Patient Care><Patient Care Delivery><Patient risk><Patients><Pattern><Penetrance><Peripheral Blood Cell><Phenotype><Physicians><Policies><Population><Population Sciences><Predicting Risk><Prevention><Principal Investigator><Probability><R & D><R&D><Refractory Anemia with an Excess of Blasts><Refractory anaemia with excess blasts><Research><Rheumatic Diseases><Rheumatism><Rheumatologic Diseases><Rheumatologic Disorder><Rheumatology><Risk><Role><SEER Program><SEER-Surveillance, Epidemiology, and End Results><Scientist><Smoldering Leukemia><Somatic Mutation><Specificity><Statistical Algorithm><Statistics Algorithm><Surveillance, Epidemiology and End Results><Surveillance, Epidemiology, and End Results Program><Symptoms><Syndrome><System><Task Forces><Temporal Arteritis><Therapeutic><Time><Title 18><Translational Research><Translational Science><Work><Writing><acute granulocytic leukemia><acute myeloid leukemia><adverse consequence><adverse outcome><advisory team><age associated><age correlated><age dependent><age linked><age related><age specific><anamnestic reaction><arthritic><biobank><biorepository><blood cancer><blood cell formation><blood cell progenitor><blood progenitor><blood stem cell><blood stem cell expansion><blood-forming stem cell><burden of disease><burden of illness><cancer of blood><cancer of the blood><cancer risk><care for patients><care of patients><career><career development><caring for patients><case-controlled studies><clinical care><clinical phenotype><clinical practice><co-morbid><co-morbidity><cohort><comorbidity><cytopenia><data base><data depository><data repository><data set repository><dataset repository><design><designing><developmental><disease burden><disease phenotype><electronic health care record><electronic health medical record><electronic health plan record><electronic health registry><electronic medical health record><forecasting risk><genetic epidemiologic study><genetic epidemiology><genome mutation><genomic data><genomic data-set><genomic dataset><health insurance for disabled><hematopoietic progenitor><hematopoietic stem cell expansion><hematopoietic stem progenitor cell><hemopoietic progenitor><hemopoietic stem cell><immune microenvironment><immunosuppressive microenvironment><immunosuppressive tumor microenvironment><improved><interventional strategy><large data sets><large datasets><leukemia><malignancy><mortality><multimorbidity><multiple chronic conditions><myelodysplasia><myeloproliferative neoplasm><neoplasm/cancer><nonmalignant><novel><precancer><precancerous><predict risk><predict risks><predicted risk><predicted risks><predicting risks><predictive risk><predictive tools><predicts risk><premalignant><prevent><preventing><research and development><risk prediction><risk prediction algorithm><risk prediction model><risk predictions><secondary immune response><social role><somatic variant><systemic inflammation><systemic inflammatory response><therapeutically effective><translation research><translational investigation><translational investigator><translational researcher><translational scientist><tumor immune microenvironment><tumor-immune system interactions>