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Medline ® Abstract for Reference 218

of '慢性髓系白血病的细胞和分子生物学'

Short interfering RNA (siRNA) targeting the Lyn kinase induces apoptosis in primary, and drug-resistant, BCR-ABL1(+) leukemia cells.
Ptasznik A, Nakata Y, Kalota A, Emerson SG, Gewirtz AM
Nat Med. 2004;10(11):1187. 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.
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