title: Targeting of BCR-ABL: Lessons learned from BCR-ABL inhibition.
abstract: In 1960 researchers reported that balanced translocation between chromosomes 22 and 9 resulted in the generation of Philadelphia chromosome. This breakthrough revolutionized our knowledge related to leukemia biology and contemporary studies revealed that chromosomal translocation resulted in the fusion between the 5' segment of BCR gene and 3' segment of the ABL gene to form BCR/ABL fusion gene. Research over the years has progressively and systematically improved our understanding of the genetic and proteomic basis of Leukemia. Genome-wide profiling studies, including genome sequencing and microarray analysis, have helped us in identification of different intracellular signaling cascades that are frequently mutated in Leukemia.  We partition this multi-component review into different sections related to biochemical characteristics of BCR-ABL+ cells, underlying mechanism of generation of mutations and crosstalk of BCR-ABL with various intracellular signaling cascades. We also summarize how BCR-ABL encoding mRNA is negatively regulated by different miRNAs and the strategies which are currently being used to effectively target BCR-ABL protein. We also provide an overview of the natural products which have been used for targeting of BCR-ABL protein. Better understanding of the protein network of Philadelphia positive leukemic cells will prove to be helpful in getting a step closer to personalized medicine.
authors.affiliation: Department of Pharmacology, Southwest Medical University, Sichuan, Luzhou 646000, China.
authors.forename: X
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Chemistry, GC University, Lahore, Pakistan.
authors.forename: M Z
authors.initials: MZ
authors.lastname: Qureshi
authors.affiliation: Yeditepe University Medical School, İnönü Mah., Kayışdağı Cad., 26 Ağustos Yerleşimi, 34755 Ataşehir/İstanbul, Turkey.
authors.forename: R
authors.initials: R
authors.lastname: Attar
authors.affiliation: Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, Pakistan.
authors.forename: S
authors.initials: S
authors.lastname: Khalid
authors.affiliation: Department of Zoology, GC University, Lahore, Pakistan.
authors.forename: F
authors.initials: F
authors.lastname: Tahir
authors.affiliation: Department of Zoology, GC University, Lahore, Pakistan.
authors.forename: A
authors.initials: A
authors.lastname: Yaqub
authors.affiliation: Department of Microbiology, Faculty of Biological Sciences, QAU, Islamabad, Pakistan.
authors.forename: A
authors.initials: A
authors.lastname: Aslam
authors.affiliation: Aziz Sancar Institute of Experimental Medicine, İstanbul University, İstanbul , Turkey.
authors.forename: I
authors.initials: I
authors.lastname: Yaylim
authors.affiliation: Biogenetika, Individualized Medicine, Florianópolis, Santa Catarina, Brazil.
authors.forename: L K
authors.initials: LK
authors.lastname: De Carlos Back
authors.affiliation: Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan. ammadfarooqi@rlmclahore.com.
authors.forename: A A
authors.initials: AA
authors.lastname: Farooqi
authors.affiliation: Institute of Biomedical and genetic Engineering (IBGE), Islamabad, Pakistan.
authors.forename: M
authors.initials: M
authors.lastname: Ismail
mesh_terms: D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D014178:Translocation, Genetic; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; D035683:MicroRNAs; D051880:Receptors, Notch; C509239:SHH protein, human; D051153:Wnt Proteins; D016044:Fusion Proteins, bcr-abl