While at Rome miRNA and TRAIL Do Whatever BCR-ABL Commands to Do
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REVIEW
While at Rome miRNA and TRAIL Do Whatever BCR-ABL Commands to Do Ammad Ahmad Farooqi • Ali Nawaz • Zeeshan Javed Shahzad Bhatti • Muhammad Ismail
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Received: 26 January 2012 / Accepted: 20 August 2012 / Published online: 11 December 2012 Ó L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2012
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. BCRABL-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 contextspecific 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-ABLpositive 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
A. A. Farooqi (&) Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College (RLMC), 35 km Ferozepur Road, Lahore, Pakistan e-mail: [email protected] A. Nawaz Z. Javed S. Bhatti IMBB, The University of Lahore, Lahore, Pakistan M. Ismail Institute of Biomedical and Genetic Engineering, Islamabad, Pakistan
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. Keywords Cancer
BCR-ABL TRAIL miRNA Apoptosis
Introduction Leukemia is characterized by hallmark features including recurring chromosomal aberrations and gene mutations that are fundamental to disease progression and pathogenesis. A supplementary layer of complexity is the role of tumor suppressor microRNAs (miRNAs) and oncomirs in leukemias. It is becoming progressively more prominent by various documentations that BCR-ABL signaling network shows a modular and layered organization. Furthermore, this mo
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