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

A Ptasznik, Y Nakata, A Kalota, SG Emerson… - Nature medicine, 2004 - nature.com
A Ptasznik, Y Nakata, A Kalota, SG Emerson, AM Gewirtz
Nature medicine, 2004nature.com
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 …
Abstract
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.
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