Short interfering RNA (siRNA) targeting the Lyn kinase induces apoptosis in primary, and drug-resistant, BCR-ABL1(+) leukemia cells.
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.
Ptasznik
Andrzej
A
Division of Hematology/Oncology, Department of Medicine and Abramson Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA. andrzejp@mail.med.upenn.edu
Nakata
Yuji
Y
Kalota
Anna
A
Emerson
Stephen G
SG
Gewirtz
Alan M
AM
D017209:Apoptosis / Q000502:physiology*; D001752:Blast Crisis / Q000378:metabolism*; D015153:Blotting, Western; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism*
D034741:RNA, Small Interfering; D013778:Tetrazolium Salts; D013844:Thiazoles; D016044:Fusion Proteins, bcr-abl; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; C022616:thiazolyl blue