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Leukemia ; 31(7): 1513-1524, 2017 07.
Article in English | MEDLINE | ID: mdl-28210003

ABSTRACT

Two major types of leukemogenic BCR-ABL fusion proteins are p190BCR-ABLand p210BCR-ABL. Although the two fusion proteins are closely related, they can lead to different clinical outcomes. A thorough understanding of the signaling programs employed by these two fusion proteins is necessary to explain these clinical differences. We took an integrated approach by coupling protein-protein interaction analysis using biotinylation identification with global phosphorylation analysis to investigate the differences in signaling between these two fusion proteins. Our findings suggest that p190BCR-ABL and p210BCR-ABL differentially activate important signaling pathways, such as JAK-STAT, and engage with molecules that indicate interaction with different subcellular compartments. In the case of p210BCR-ABL, we observed an increased engagement of molecules active proximal to the membrane and in the case of p190BCR-ABL, an engagement of molecules of the cytoskeleton. These differences in signaling could underlie the distinct leukemogenic process induced by these two protein variants.


Subject(s)
Fusion Proteins, bcr-abl/physiology , Signal Transduction/physiology , Cytoskeletal Proteins/metabolism , Humans , Leukemia/etiology , Phosphorylation , STAT Transcription Factors/physiology
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