Unbiased, systematic surfaceome profiling of Acute Leukemia to identify novel immunotherapy targets
- 1Boston Children's Hospital
Abstract
Cell surface proteomics provides a direct topological assessment of the outer membrane of cells and enables the capture of low abundance proteins that may be missed by whole cell proteomics. Here we present an unbiased atlas of the whole cell and surface proteomes of 25 commonly used leukemic cell lines, encompassing both lymphoid and myeloid lineages, and a variety of driver mutations. Paired-wise analysis highlights recurrent surface proteins that are not detected by whole cell proteomics. Coupling this dataset to RNA-sequencing, we also discovered genes where protein and RNA abundances are discordant. In KMT2A-rearranged AML, CD70 expression was increased across cell lines and validated in primary patient samples, supporting CD70 as a candidate therapeutic target in this disease. Several proteins are enriched in the surface proteomes but lack surface annotation, adding to the growing list of potential non-canonical cell surface proteins. These findings reveal a substantial pool of proteins absent from conventional surface annotations, including RNA-binding proteins, an emerging class of candidate immunotherapeutic targets.
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BibTeX
@misc{george2026unbiased,
title = {{Unbiased, systematic surfaceome profiling of Acute Leukemia to identify novel immunotherapy targets}},
author = {B. M. George and A. Rodriguez-Pohnlein and D. J. DeCastro and J. Porat and B. Zhao and D. M. Abeja and R. J. Lumpkin and R. J. Metivier and A. Schmoker and W. Walter and T. Haferlach and Y. M. Pikman and K. Donovan and K. Stegmaier and E. S. Fischer and F. Wachter and R. A. Flynn},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.16.752145},
url = {https://www.biorxiv.org/content/10.64898/2026.09.16.752145v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Unbiased, systematic surfaceome profiling of Acute Leukemia to identify novel immunotherapy targets
AU - B. M. George
AU - A. Rodriguez-Pohnlein
AU - D. J. DeCastro
AU - J. Porat
AU - B. Zhao
AU - D. M. Abeja
AU - R. J. Lumpkin
AU - R. J. Metivier
AU - A. Schmoker
AU - W. Walter
AU - T. Haferlach
AU - Y. M. Pikman
AU - K. Donovan
AU - K. Stegmaier
AU - E. S. Fischer
AU - F. Wachter
AU - R. A. Flynn
PY - 2026
DA - 2026/09/16
PB - bioRxiv
DO - 10.64898/2026.09.16.752145
UR - https://www.biorxiv.org/content/10.64898/2026.09.16.752145v1
AB - Cell surface proteomics provides a direct topological assessment of the outer membrane of cells and enables the capture of low abundance proteins that may be missed by whole cell proteomics. Here we present an unbiased atlas of the whole cell and surface proteomes of 25 commonly used leukemic cell lines, encompassing both lymphoid and myeloid lineages, and a variety of driver mutations. Paired-wise analysis highlights recurrent surface proteins that are not detected by whole cell proteomics. Coupling this dataset to RNA-sequencing, we also discovered genes where protein and RNA abundances are discordant. In KMT2A-rearranged AML, CD70 expression was increased across cell lines and validated in primary patient samples, supporting CD70 as a candidate therapeutic target in this disease. Several proteins are enriched in the surface proteomes but lack surface annotation, adding to the growing list of potential non-canonical cell surface proteins. These findings reveal a substantial pool of proteins absent from conventional surface annotations, including RNA-binding proteins, an emerging class of candidate immunotherapeutic targets.
ER -