Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones

Cancer Cell
Bauke de BoerJan Jacob Schuringa

Abstract

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.

Citations

Nov 26, 2019·Current Protocols in Cytometry·Wendelien ZeijlemakerGerrit Jan Schuurhuis
Jan 8, 2020·Nature Reviews. Cancer·David VetrieMhairi Copland
Jun 25, 2020·EMBO Molecular Medicine·Renata StripeckeLeonard Shultz
Dec 24, 2018·Nature Reviews. Cancer·Uri Ben-DavidTodd R Golub
Sep 1, 2019·International Journal of Molecular Sciences·Peter ValentDominik Wolf
Sep 23, 2020·International Journal of Molecular Sciences·Maria Hernandez-ValladaresFrode Selheim
Dec 16, 2020·Cancer Cell·Jan Jacob Schuringa, Constanze Bonifer
Jan 4, 2021·Stem Cell Research·Nikolaos Spyrou, Eirini P Papapetrou
Jan 10, 2021·Molecular Oncology·Myint Myat Khine AungKaren Keeshan
Jan 30, 2021·The FEBS Journal·Benjamin Edginton-White, Constanze Bonifer
Feb 1, 2021·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Mohammad AbbasJeffrey A Stuart
Jan 13, 2021·Nature Communications·Anne-Louise LatifPeter D Adams
May 11, 2021·Molecular & Cellular Proteomics : MCP·Carolina Hassibe ThoméVitor M Faça
Jul 25, 2021·International Journal of Molecular Sciences·Daniel CacicTor Hervig
Jun 12, 2021·Blood·Jeffrey E Rubnitz, Gertjan J L Kaspers

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