Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclonesde Boer, B., Prick, J., Pruis, M. G., Keane, P., Imperato, M. R., Jaques, J., Brouwers-Vos, A. Z., Hogeling, S. M., Woolthuis, C. M., Nijk, M. T., Diepstra, A., Wandinger, S., Versele, M., Attar, R. M., Cockerill, P. N., Huls, G., Vellenga, E., Mulder, A. B., Bonifer, C. & Schuringa, J. J., 8-Oct-2018, In : Cancer cell. 34, 4, p. 674-+ 24 p.
Research output: Contribution to journal › Article › Academic › peer-review
Intra-tumor heterogeneity caused by clonal evolution is a major problem in cancer treatment. To address this problem, we performed label-free quantitative proteomics on primary acute myeloid leukemia (AML) samples. We identified 50 leukemia-enriched plasma membrane proteins enabling the prospective isolation of genetically distinct subclones from individual AML patients. Subclones differed in their regulatory phenotype, drug sensitivity, growth, and engraftment behavior, as determined by RNA sequencing, DNase I hypersensitive site mapping, transcription factor occupancy analysis, in vitro culture, and xenograft transplantation. Finally, we show that these markers can be used to identify and longitudinally track distinct leukemic clones in patients in routine diagnostics. Our study describes a strategy for a major improvement in stratifying cancer diagnosis and treatment.
|Number of pages||24|
|Early online date||20-Sep-2018|
|Publication status||Published - 8-Oct-2018|
- ACUTE MYELOID-LEUKEMIA, GENE-EXPRESSION PROFILES, HEMATOPOIETIC STEM-CELLS, CLONAL HEMATOPOIESIS, INITIATING CELLS, MLL-AF9 LEUKEMIA, PROGENITOR CELLS, MODEL ENABLES, MOUSE MODELS, TARGET GENES