Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones

被引：73

作者：

de Boer, Bauke ^{[1
]}

Prick, Janine ^{[1
]}

Pruis, Maurien G. ^{[1
]}

Keane, Peter ^{[2
]}

Imperato, Maria Rosaria ^{[2
]}

Jaques, Jennifer ^{[1
]}

Brouwers-Vos, Annet Z. ^{[1
]}

Hogeling, Shanna M. ^{[1
]}

Woolthuis, Carolien M. ^{[1
]}

Nijk, Marije T. ^{[3
]}

Diepstra, Arjan ^{[4
]}

Wandinger, Sebastian ^{[5
]}

Versele, Matthias ^{[6
]}

Attar, Ricardo M. ^{[6
]}

Cockerill, Peter N. ^{[2
]}

Huls, Gerwin ^{[1
]}

Vellenga, Edo ^{[1
]}

Mulder, Andre B. ^{[3
]}

Bonifer, Constanze ^{[2
]}

Schuringa, Jan Jacob ^{[1
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, CRCG, Dept Expt Hematol, Hanzepl 1,DA13, NL-9700 RB Groningen, Netherlands

[2] Univ Birmingham, Coll Med & Dent, Inst Canc & Genom Sci, Birmingham B15 2TT, W Midlands, England

[3] Univ Groningen, Univ Med Ctr Groningen, Dept Lab Med, Hanzepl 1, NL-9700 RB Groningen, Netherlands

[4] Univ Groningen, Univ Med Ctr Groningen, Dept Pathol & Med Biol, Hanzepl 1, NL-9700 RB Groningen, Netherlands

[5] Evotec Munchen GmbH, Klopferspitz 19a, D-82152 Martinsried, Germany

[6] Janssen Res & Dev, Turnhoutseweg 30, B-2340 Beerse, Belgium

来源：

CANCER CELL | 2018年 / 34卷 / 04期

基金：

欧洲研究理事会;

关键词：

ACUTE MYELOID-LEUKEMIA; GENE-EXPRESSION PROFILES; STEM-CELLS; CLONAL HEMATOPOIESIS; PROGENITOR CELLS; MODEL ENABLES; MOUSE MODELS; TARGET GENES; LABEL-FREE; IDENTIFICATION;

D O I：

10.1016/j.ccell.2018.08.014

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：674 / +

页数：24

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