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Kinase activity profiling reveals active signal transduction pathways in pediatric acute lymphoblastic leukemia: a

Naomi E van der Sligte1, Frank J G Scherpen, Tiny G J Meeuwsen-de Boer

  • 1Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Proteomics
|November 26, 2014
PubMed

Insights

Kinome profiling reveals key signaling pathways in pediatric acute lymphoblastic leukemia (ALL). This approach identifies potential drug targets to address treatment resistance in ALL patients.

Area of Science:

  • Oncology
  • Biochemistry
  • Molecular Biology

Background:

  • Approximately 20% of acute lymphoblastic leukemia (ALL) patients experience relapse despite intensive chemotherapy.
  • Kinase activity profiling offers insights into active signaling pathways and potential therapeutic targets in ALL.
  • Identifying novel druggable targets is crucial for bridging the gap between drug development and ALL treatment.

Purpose of the Study:

  • To perform kinome profiling on pediatric ALL samples to identify signaling proteins relevant to the disease.
  • To characterize activated signaling pathways in both B-cell precursor ALL (BCP-ALL) and T-cell ALL (T-ALL).
  • To identify differentially phosphorylated peptides between BCP-ALL and T-ALL for potential targeted therapy.

Main Methods:

  • Kinome profiling was conducted on 20 pediatric ALL samples (14 BCP-ALL, 6 T-ALL).
  • Peptide phosphorylation was analyzed to identify commonly activated and differentially phosphorylated signaling proteins.
  • The efficacy of a selected target (HGFR_Y1235) was tested as a proof of principle.

Main Results:

  • 250 peptides were commonly activated in both BCP-ALL and T-ALL, involving MAPK, PI3K/Akt, and cell cycle/p53 pathways.
  • 27 peptides showed differential phosphorylation between BCP-ALL and T-ALL.
  • Ten peptides were more phosphorylated in BCP-ALL, and 17 were more phosphorylated in T-ALL.

Conclusions:

  • Kinome profiling is an effective method for studying active signaling in ALL.
  • This technique can identify potential druggable targets for ALL treatment.
  • Targeting specific signaling pathways may help overcome resistance in ALL.
Keywords:
Acute lymphoblastic leukemiaHGFRKinome profilingProtein arraysRONSignal transduction

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