Short interfering RNA (siRNA) targeting the Lyn kinase induces apoptosis in primary, and drug-resistant, BCR-ABL1(+) leukemia cells

Nat Med. 2004 Nov;10(11):1187-9. doi: 10.1038/nm1127. Epub 2004 Oct 24.


We studied the effects of Lyn ablation on the survival of drug-resistant chronic myelogenous leukemia (CML) blast crisis cells using siRNA. Lyn siRNA reduced Lyn protein in both normal hematopoietic cells and BCR-ABL1-expressing (BCR-ABL1(+)) blasts by 80-95%. Within 48 h, siRNA-treated BCR-ABL1(+) blasts underwent apoptosis, whereas normal cells remained viable. This increased dependence on Lyn signaling for BCR-ABL1(+) blast survival provides the basis for rational treatment of drug-resistant CML blast crisis, particularly when lymphoid in nature.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis / physiology*
  • Blast Crisis / metabolism*
  • Blotting, Western
  • Fusion Proteins, bcr-abl / metabolism*
  • Humans
  • In Situ Nick-End Labeling
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism*
  • RNA, Small Interfering / physiology
  • Signal Transduction / physiology
  • Tetrazolium Salts
  • Thiazoles
  • Tumor Cells, Cultured
  • src-Family Kinases / metabolism*


  • RNA, Small Interfering
  • Tetrazolium Salts
  • Thiazoles
  • Fusion Proteins, bcr-abl
  • lyn protein-tyrosine kinase
  • src-Family Kinases
  • thiazolyl blue