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Complex exon structure of CD19 and CD22 mRNA isoforms revealed by long-read Oxford Nanopore sequencing

Mukta Asnani

Mukta Asnani, Children's Hospital of Philadelphia

Abstract

Novel immunotherapies directed against B-cell restricted surface antigens CD19 and CD22 are used successfully for the treatment of relapsed acute lymphoblastic leukemias (B-ALL), but acquired resistance is emerging as a major barrier. Our previous studies indicated that alternative splicing of CD19 could contribute to epitope loss and treatment failures. Here we utilized the Oxford Nanopore Technologies platform to determine complete exon structures of CD19 and CD22 transcripts in B-ALL cell lines and patient-derived xenografts. We discovered that many (but not all of them) encode functional proteins capable of conferring resistance to immunotherapy such as CAR T-cells.

Bio

Mukta Asnani is currently working as a postdoctoral fellow at the Children’s Hospital of Philadelphia, PA. She earned her M.S. in Biotechnology from New York University, NY, and her Ph.D. in Molecular and Cellular Biology from SUNY Downstate Medical Center, NY. She has over nine years of experience in molecular biology, RNA biochemistry, and oncology. Currently, under the tutelage of Dr. Andrei Thomas-Tikhonenko, she is involved in studying the mechanisms of resistance to novel immunotherapies for pediatric leukemias