Titles + affiliations
Assistant Professor, Division of Hematology
The Ohio State University
Research
Understanding Poor Survival and Treatment Resistance in Young Black NPM1-Mutated Patients with Acute Myeloid Leukemia
Summary
Acute myeloid leukemia (AML) is an aggressive blood cancer, of which only ~25% of patients are currently cured despite modern therapies. It became clear over the past years that the cancer cells of leukemia patients respond differently to available treatments based on differences in the molecular underpinnings of the cells. We recently performed the thus far largest study that examined the outcomes of Black patients diagnosed with AML compared to White patients with similar characteristics. Notably, both in a population-based study and in the setting of clinical trials, Black patients fared worse with ~40% higher chances to die from their disease compared to White patients. Unexpectedly, the survival discrepancy was highest in the molecular “favorable” risk group of patients harboring gene mutations in a gene called NPM1, thereby suggesting differences in disease biology that affect treatment response, and specifically the ability of standard chemotherapy to eradicate the leukemic clone based on the constitutional contributors associated with a patient’s race. Our proposal is designed to further understand the underlying mechanisms for the survival discrepancy and treatment response specifically in the “favorable” risk group, based on the overarching hypothesis that race-associated genetic features cause differential molecular/pathologic responses to treatment in Black and White AML patients.
Impact
We successfully analyzed the genetic and genomic content of leukemic cells of African-American patients with AML. We focused on patients harboring mutations in the known leukemia-associated gene NPM1c. This population was chosen since it is thought to carry a favorable response to cytotoxic chemotherapy, based on routinely used clinical guidelines. However, we show that in African-American patients, NPM1c is actually an adverse-risk marker and patients should receive different treatment. In the comprehensive molecular analyses we found new genetic variants that might contribute to differences in the treatment response; and show that most patients after chemotherapy still have residual disease, confirming insufficient treatment with current measures.
Excitingly, we utilized the preliminary data acquired via Leukemia Research Foundation funding to apply for Federal funding, and just received confirmation about $3M in funding support from the National Cancer Institute. Now, we will be able to test which of these newly discovered variants matter most for patients and potentially work towards new drug targets.
Leukemia Research Foundation was the first to believe in the importance to understand genetic and genomic contributors to health inequities in leukemia patients. This sets an important milestone for equity and inclusivity in care. Since then, our results support its importance, but we still have a long way to go until we understand AML across all ancestral backgrounds the same way. In parallel, we need to address structural racism and socioeconomic contributors, all of which contribute to survival inequities and who are interconnected.
Publications
Leukemia Research Foundation grant
$100K awarded in 2021
Disease focus
Acute myeloid leukemia (AML)
Research focus
Causes/risk factors (genetics)