Invited Research Meeting - Prof. Kara Davis - Predicting Patient Outcomes from Single Cells in Childhood Leukemia

11 Aprile 2022, ore 15:00

Seminario in presenza con possibilità di collegamento webex da remoto

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Lunedì 11 Aprile 2022, ore 13

Edificio Asclepio U8-Aula 4

Seminario in presenza con possibilità di collegamento da remoto

Online Webex https://unimib.webex.com/unimib-it/j.php?MTID=m34ebe311f80a099eb78193f374bf7897

Host: Prof. Giovanni Cazzaniga

Abstract

Insight into the cancer cell populations that are responsible for relapsed disease is needed to improve outcomes. Our recent studies reported a single-cell-based study of B cell precursor acute lymphoblastic leukemia at diagnosis that reveals hidden developmentally dependent cell signaling states that are uniquely associated with relapse. By using CyTOF, we simultaneously quantified several proteins involved in B cell development in diagnostic samples and then matched to its nearest healthy B cell population at the single-cell level. Machine learning identified features to predict patients’ relapse at diagnosis and allowed the setup a predictive model, significantly improving currently established risk stratification methods.

Further in B-cell onco-hematology field, the advanced treatments are nowadays focused on CD19-directed chimeric antigen receptor T cell (CAR-T) therapy, which has shown impressive results in children and adults with relapsed or refractory B-ALL or diffuse large B-cell lymphoma. However, 30-70% of initial responders will eventually relapse with CD19 antigen loss and CD19Neg relapses also occur in patients treated with other CD19-directed immunotherapies, like blinatumomab.

Thus, our efforts are focused on a predictive model to detect patients at risk of CD19Neg relapse, which would have broader therapeutic impact.

Overall, by leveraging a data-driven approach, we demonstrate the predictive value of single-cell 'omics' for patient stratification in a translational setting and provide a framework for its application to human cancer.

Guest

Kara Davis, D.O. is an Assistant Professor of Pediatrics in the Division of Hematology and Oncology. Dr. Davis obtained her B.A. from Pennsylvania State University and her D.O. from the Philadelphia College of Osteopathic Medicine.

Clinically, she completed her training in Pediatrics at Thomas Jefferson University/A.I. DuPont Children’s Hospital and her Heme/Onc fellowship at Lucile Packard Children’s Hospital at Stanford. During her fellowship training, Kara worked in the laboratory of Garry Nolan, Ph.D. where she utilized single-cell, high-dimensional analysis platforms to study healthy human B cell development and B cell leukemia.

Her research focuses on using single-cell analysis to organize tumor heterogeneity in pediatric cancers, especially blood cancers, as means to determine cell populations associated with clinical risks such as relapse. Clinically, Dr. Davis sees patients with leukemia and is involved with the Cancer Cellular Therapies program with experience in treating children with chimeric antigen receptor (CAR) T-cells and other immunotherapies including checkpoint inhibitors.

Locandina/Flyer Kara Davis 110422