Gene Expression Profiles Associated with Pediatric Relapsed AML

PLoS One

Ursula Creutzig¹  Valérie de Haas¹  Gerrit Jan Schuurhuis²  C. Michel Zwaan²  Eveline S. J. M. de Bont³  Monique L. den Boer³  Marry M. van den Heuvel-Eibrink³  Costa Bachas⁴  Jacqueline Cloos⁴  Dirk Reinhardt⁴  Zinia J. Kwidama⁵  Gertjan J. L. Kaspers⁶ 

[1] AML-BFM Study Group, Department of Pediatric Hematology/ Oncology, Medical School Hannover, Hannover, Germany;Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands;Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children’s Hospital, Rotterdam, The Netherlands;Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands;Division of Pediatric Oncology/Hematology, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands;Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands

关键词: Gene expression;    Acute myeloid leukemia;    Transcription factors;    Pediatrics;    Histones;    Cytogenetics;    DNA transcription;    Cancer treatment;   

DOI  :  10.1371/journal.pone.0121730

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Development of relapse remains a problem for further improvements in the survival of pediatric AML patients. While virtually all patients show a good response to initial treatment, more patients respond poorly when treated at relapse. The cellular characteristics of leukemic blast cells that allow survival of initial treatment, relapse development and subsequent resistance to salvage treatment remain largely elusive. Therefore, we studied if leukemic blasts at relapse biologically resemble their initial diagnosis counterparts. We performed microarray gene expression profiling on paired initial and relapse samples of 23 pediatric AML patients. In 11 out of 23 patients, gene expression profiles of initial and corresponding relapse samples end up in different clusters in unsupervised analysis, indicating altered gene expression profiles. In addition, shifts in type I/II mutational status were found in 5 of these 11 patients, while shifts were found in 3 of the remaining 12 patients. Although differentially expressed genes varied between patients, they were commonly related to hematopoietic differentiation, encompassed genes involved in chromatin remodeling and showed associations with similar transcription factors. The top five were CEBPA, GFI1, SATB1, KLF2 and TBP. In conclusion, the leukemic blasts at relapse are biologically different from their diagnosis counterparts. These differences may be exploited for further development of novel treatment strategies.

【 授权许可】

CC BY