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


Authors >Ptasznik A, >Nakata Y, >Kalota A, >Emerson SG, >Gewirtz AM
In >Nat Med (2004) 10(11): 1187-1189
Cells used in publication HL-60 (ATCC)
   Blood/Immune Cells
   Cell Lines
   Species: human
   Tissue Origin: blood
K-562 (ATCC)
   Blood/Immune Cells
   Cell Lines
   Species: human
   Tissue Origin: blood
T cell, stim., human
   Human stimulated T cells
   Blood/Immune Cells
   Primary Cells
   Species: human
   Tissue Origin: blood
CD34+ cell, human
   Human CD34+ hematopoietic progenitor cells
   Stem Cells
   Primary Cells
   Species: human
   Tissue Origin: blood
LAMA-84
   Blood/Immune Cells
   Cell Lines
   Species: human
   Tissue Origin: blood
M-07e
   Blood/Immune Cells
   Cell Lines
   Species: human
   Tissue Origin: blood
EM2
   Blood/Immune Cells
   Cell Lines
   Species: human
EM3
   Blood/Immune Cells
   Cell Lines
   Species: human
Substrate siRNA
Applications >RNAi
>Co-Transfection
Topics >Apoptosis
>Diseases (e.g. HIV)
>Microscopy of nucleofected cells
>Signal transduction
Research Areas >Cancer Research/Cell Biology
>Immunology / Hematology
Relevant Products > Nucleofector Device

Research Field

Leukemias that express the oncoprotein BCR-ABL1 are resistant to apoptotic stimuli, and are relatively insensitive to chemotherapy. However, they show an increased dependence on Lyn signaling for survival, which provides the basis for rational treatment. Lyn is a kinase that interacts with BCR-ABL1 in signaling complexes.

Nucleofection Experiments

Lyn siRNA was transfected into different human primary cells (CD34+ cells, leukemic blasts) and cell lines (K562, HL-60, EM2, EM3, LAMA84, Mo7e). In all cells that express BCR-ABL1 (leukemic blasts from patients; K562, EM2, EM3, LAMA84) Lyn knock-down led to apoptosis, all cells not expressing BCR-ABL1 (normal CD34+ cells; Mo7e) did not go into apoptosis upon Lyn knock-down.
In a rescue experiment for the apoptosis phenotype K562 cells were cotransfected with siRNA to the 3’UTR of Lyn mRNA together with a Lyn expression construct lacking the 3’UTR.

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