title: Gene expression profiles associated with pediatric relapsed AML.
abstract: 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.
authors: Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands; Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Costa
authors: C
authors: Bachas
authors: Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Gerrit Jan
authors: GJ
authors: Schuurhuis
authors: Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
authors: C Michel
authors: CM
authors: Zwaan
authors: Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
authors: Marry M
authors: MM
authors: van den Heuvel-Eibrink
authors: Department of Pediatric Oncology/Hematology, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
authors: Monique L
authors: ML
authors: den Boer
authors: Division of Pediatric Oncology/Hematology, Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors: Eveline S J M
authors: ES
authors: de Bont
authors: Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Zinia J
authors: ZJ
authors: Kwidama
authors: AML-BFM Study Group, Department of Pediatric Hematology/ Oncology, Medical School Hannover, Hannover, Germany.
authors: Dirk
authors: D
authors: Reinhardt
authors: AML-BFM Study Group, Department of Pediatric Hematology/ Oncology, Medical School Hannover, Hannover, Germany.
authors: Ursula
authors: U
authors: Creutzig
authors: Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands.
authors: Valérie
authors: V
authors: de Haas
authors: Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands; Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands.
authors: Gertjan J L
authors: GJ
authors: Kaspers
authors: Department of Pediatric Oncology/Hematology, VU University Medical Center, Amsterdam, The Netherlands; Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
authors: Jacqueline
authors: J
authors: Cloos
mesh_terms: D000293:Adolescent; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012008:Recurrence
chemical_list: D009363:Neoplasm Proteins