title: While at Rome miRNA and TRAIL do whatever BCR-ABL commands to do.
abstract: It is a well-acclaimed fact that proteins expressed as a consequence of oncogenic fusions, mutations or amplifications can facilitate ectopic protein-protein interactions that re-wire signal dissemination pathways, in a manner that escalates malignancy. BCR-ABL-mediated signal transduction cascades in leukemic cells are assembled and modulated by a finely controlled network of protein-protein interactions, mediated by characteristic signaling domains and their respective binding motifs. BCR-ABL functions in a cell context-specific and cell type-specific manner to integrate signals that affect uncontrolled cellular proliferation. In this review, we draw attention to the recent progress made in outlining resistance against TRAIL-mediated apoptosis and diametrically opposed roles of miRNAs in BCR-ABL-positive leukemic cells. BCR-ABL governs carcinogenesis through well-organized web of antiapoptotic proteins and over-expressed oncomirs which target death receptors and pro-apoptotic genes. Set of oncomirs which inversely correlate with expression of TRAIL via suppression of SMAD is an important dimension which is gradually gaining attention of the researchers. Contrary to this, some current findings show a new role of BCR-ABL in nucleus with spotlight on apoptosis. It seems obvious that genetic heterogeneity of leukemias poses therapeutic challenges, and pharmacological agents that target components of the cancer promoting nano-machinery still need broad experimental validation to be considered competent as a component of the therapeutic arsenal for this group of diseases. Rapidly developing technologies are empowering us to explain the molecular "nature" of a patient and/or tumor and with this integration of personalized medicine, with maximized efficacy, cost effectiveness will hopefully improve survival chances of the patient.
authors.affiliation: Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College (RLMC), Lahore, Pakistan. ammadahmad638@yahoo.com
authors.forename: Ammad Ahmad
authors.initials: AA
authors.lastname: Farooqi
authors.forename: Ali
authors.initials: A
authors.lastname: Nawaz
authors.forename: Zeeshan
authors.initials: Z
authors.lastname: Javed
authors.forename: Shahzad
authors.initials: S
authors.lastname: Bhatti
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ismail
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D057285:Precision Medicine; D051785:Smad Proteins / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D051785:Smad Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D016044:Fusion Proteins, bcr-abl