TY - JOUR
T1 - Gene expression profiles associated with pediatric relapsed AML
AU - Bachas, Costa
AU - Schuurhuis, Gerrit Jan
AU - Zwaan, C Michel
AU - van den Heuvel-Eibrink, Marry M
AU - den Boer, Monique L
AU - de Bont, Eveline S J M
AU - Kwidama, Zinia J
AU - Reinhardt, Dirk
AU - Creutzig, Ursula
AU - de Haas, Valérie
AU - Kaspers, Gertjan J L
AU - Cloos, Jacqueline
N1 - Publisher Copyright:
Copyright: © 2015 Bachas et al.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - Adolescent
KW - Female
KW - Follow-Up Studies
KW - Gene Expression Profiling
KW - Gene Expression Regulation, Leukemic
KW - Humans
KW - Leukemia, Myeloid, Acute/genetics
KW - Male
KW - Neoplasm Proteins/biosynthesis
KW - Recurrence
UR - http://www.scopus.com/inward/record.url?scp=84929492278&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0121730
DO - 10.1371/journal.pone.0121730
M3 - Article
C2 - 25849371
SN - 1932-6203
VL - 10
SP - e0121730
JO - PloS one
JF - PloS one
IS - 4
M1 - 0121730
ER -