Identification of genes associated with chemotherapy crossresistance and treatment response in childhood acute lymphoblastic leukemia

Sanne Lugthart, Meyling H Cheok, Monique L den Boer, Wenjian Yang, Amy Holleman, Cheng Cheng, Ching-Hon Pui, Mary V Relling, Gritta E Janka-Schaub, Rob Pieters, William E Evans

Research output: Contribution to journalArticlepeer-review

139 Citations (Scopus)


Acute lymphoblastic leukemia (ALL) can be cured with combination chemotherapy in over 75% of children, but the cause of treatment failure in the remaining patients is unknown. We determined the sensitivity of ALL cells to individual antileukemic agents in 441 patients and used a genome-wide approach to identify 45 genes differentially expressed in ALL exhibiting crossresistance to prednisolone, vincristine, asparaginase, and daunorubicin. We also identified a distinct phenotype of discordant resistance to asparaginase and vincristine and 139 genes whose expression was associated with this novel phenotype. The expression of these genes discriminated treatment outcome in two independent patient populations, identifying a subset of patients with a markedly inferior outcome (37% +/- 13% 5 year DFS).

Original languageEnglish
Pages (from-to)375-86
Number of pages12
JournalCancer cell
Issue number4
Publication statusPublished - Apr 2005
Externally publishedYes


  • Age Factors
  • Antineoplastic Agents/pharmacology
  • Asparaginase/pharmacology
  • Cell Survival/drug effects
  • Child
  • Cluster Analysis
  • Core Binding Factor Alpha 2 Subunit
  • Daunorubicin/pharmacology
  • Disease-Free Survival
  • Drug Resistance, Multiple/genetics
  • Drug Resistance, Neoplasm/genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic/drug effects
  • Homeodomain Proteins/genetics
  • Humans
  • Mercaptopurine/pharmacology
  • Neoplasm Recurrence, Local
  • Oncogene Proteins, Fusion/genetics
  • Phenotype
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
  • Predictive Value of Tests
  • Prednisolone/pharmacology
  • Principal Component Analysis
  • Proportional Hazards Models
  • Translocation, Genetic/genetics
  • Treatment Outcome
  • Tumor Cells, Cultured
  • Vincristine/pharmacology


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