By Patrick Sherry
Dr. Jatinder Lamba, a Professor and Frank A. Duckworth Eminent Chair in the Department of Pharmacotherapy and Translational Research, studies acute myeloid leukemia (AML) with the overarching goal to develop strategies to improve prognostication and therapeutic outcomes of this deadly disease.
Her research career began in the field of pharmacogenomics, inquiring about how one’s inherited genome impacts the response and effectiveness of drugs. But her interest in pursuing treatments for AML occurred while completing her postdoctoral fellowship at St. Jude Children’s Research Hospital, a nonprofit charity that provides pediatric treatment for diseases such as AML. Since then she has made strides in understanding the effectiveness of personalized treatments that can lead to a beneficial outcome for those affected by the disease.
Treatments for AML have essentially remained unchanged for more than 50 years with the primary treatment being chemotherapy using drugs cytarabine in combination with daunorubicin. Additionally, while outcomes of other forms of leukemia such as acute lymphoblastic leukemia have seen improvements in survival rates, the same cannot be said about AML. Dr. Lamba’s research, however, is interested in using genomic biomarkers to create precision, genomics-based treatment regimens to best combat the disease at the individual level.
“Understanding patients’ leukemic cells’ genomics helps us decide what is the best combination regimen that will have the best therapeutic efficacy and least toxicity in the patients,” said Lamba.
This research uses the leukemic cells that are obtained at diagnosis to generate multi-omics data (genomic, epigenomic, transcriptomic, metabolomic, and proteomics) to establish the molecular landscape of leukemic cells. This data also creates patient-specific risk classifications of prognostic and therapeutic relevance. The classifications then can be used to determine probabilities for disease relapse or death, therefore providing valuable insight into tailored treatment that can best benefit the patient.
Recently, Dr. Lamba and her research team published a paper in the Journal of Clinical Oncology, one of the highest-impact journals in the field with an impact factor of 44.54. The paper details how polygenic risk scores for patients were generated to establish personalized treatments and dosages of chemotherapy. Patients with low scores were given a higher dosage of a drug or given an additional drug to the treatment regimen. In contrast, patients with high scores when treated with lower doses had similar efficacy indicating this was a reasonable strategy to avoid toxicity. Another interesting finding from this study showed a higher abundance of poor performing low scores in patients with African ancestry thereby implying this may be one of the contributors to poor outcomes reported in this group of patients. Currently, her team is in discussions with different groups to implement these scores in clinical trials. This is all done to help further pursue personalized treatment plans.
“We have this score that can really help design the best combination regiment for the patient,” said Lamba. “With our global transcriptomics or multi-omics studies, we hope that we can identify some targets that could then be used for designing novel drugs.”
A better understanding of genomics and genetic mutations in recent years has allowed researchers like Dr. Lamba to be at the forefront of innovative discoveries that ultimately benefit those impacted by these types of diseases.
One of these pursuits as a result of her research has led to a global collaborative project in nine different countries and 20 centers in Africa. It is investigating how these genomic scores can be used to understand the discrepancies in patient outcomes between individuals of different backgrounds.
“It’s amazing, especially given the fact that this disease has such a bad outcome,” said Lamba. “It’s very important we really make some advances by using more efficacious drug genomics-guided combination so that we can improve the outcome in patients.”
Besides her research into AML, Dr. Lamba was also selected as the chair for the 2022 Florida Genetics Symposium, an event where researchers and students around the world can present and discuss topics within their field. The purpose of this significant event is to allow researchers to demonstrate their innovative findings, and most importantly, facilitate collaboration.
“I am looking forward to learning about new platforms and technologies and strategies that might hold potential in my area of research,” said Lamba, prior to the event. “That’s the purpose here – we learn from each other, collaborate, and then see what they have developed and how can that enhance my research program and vice versa.”
But overall, Dr. Lamba maintains that all these pursuits are centered around the patient, to improve the outcome of a disease that can cause so much harm.
“We do have these devastating diseases that we should look into,” said Lamba. “With exponential technological advances in recent years, we need to leverage all this to make an impact, especially for those circumstances where the outcome is really poor.”