Molecular mechanisms involved in chemoresistance in paediatric acute lymphoblastic leukaemia

Tatjana Stankovic, Eliot Marston

Research output: Contribution to journalReview article

18 Citations (Scopus)


Acute lymphoblastic leukaemia (ALL) is the most common paediatric cancer. Despite cure rates approaching 80%, resistance to treatment and disease relapse remain a significant clinical problem. Identification of the genes and biological pathways responsible for chemoresistance is therefore crucial for the design of novel therapeutic approaches aiming to improve patient survival. Mutations in the membrane transporter P-glycoprotein genes, genetic variations in drug-metabolising enzymes and defects in apoptotic pathways are mechanisms of chemoresistance common to a wide spectrum of cancers and also play a role in paediatric ALL. In addition, several recent microarray studies have identified transcriptional profiles specifically associated with chemoresistance and pointed to a number of potentially novel therapeutic targets. These microarray studies have shown that genes discriminating between clinically responsive and resistant leukaemias tend to be involved in cellular processes such as regulation of cell cycle, proliferation, and DNA repair. Here we review the outcomes of these microarray studies and also present our own investigations into apoptotic resistance to DNA double strand breaks (DSBs) in paediatric ALL. We present stratification of paediatric ALL by the profile of DNA damage response following ionising radiation (IR) in vitro. This approach allows classification of ALL tumours at presentation into IR-apoptotic sensitive and IR-apoptotic resistant. Furthermore, apoptotic resistant leukaemias exhibit abnormal response of NFkB pathway following irradiation and inhibition of this pathway can sensitise leukaemic cells to IR-induced DSBs.
Original languageEnglish
Pages (from-to)187-192
Number of pages6
JournalSrpski arhiv za celokupno lekarstvo
Issue number3-4
Publication statusPublished - 1 Mar 2008


  • chemoresistance
  • DNA damage response
  • microarray
  • ALL


Dive into the research topics of 'Molecular mechanisms involved in chemoresistance in paediatric acute lymphoblastic leukaemia'. Together they form a unique fingerprint.

Cite this