Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones

Bauke de Boer, Janine Prick, Maurien G. Pruis, Peter Keane, Maria Rosaria Imperato, Jennifer Jaques, Annet Z. Brouwers-Vos, Shanna M. Hogeling, Carolien M. Woolthuis, Marije T. Nijk, Arjan Diepstra, Sebastian Wandinger, Matthias Versele, Ricardo M. Attar, Peter N. Cockerill, Gerwin Huls, Edo Vellenga, Andre B. Mulder, Constanze Bonifer, Jan Jacob Schuringa*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

32 Citaten (Scopus)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)674-+
Aantal pagina's24
TijdschriftCancer cell
Volume34
Nummer van het tijdschrift4
Vroegere onlinedatum20-sep-2018
DOI's
StatusPublished - 8-okt-2018

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