Targeting the Oligomerization of BCR/ABL by Membrane Permeable Competitive Peptides Inhibits the Proliferation of Philadelphia Chromosome Positive Leukemic Cells

dc.contributor.authorMian, Afsar Ali
dc.contributor.authorSchull, Marion
dc.contributor.authorOancea, Claudia
dc.contributor.authorNajajreh, Yousef
dc.contributor.authorMahajna, Jamal
dc.contributor.authorGoldblum, Amiram
dc.contributor.authorOttmann, Oliver Gerhard
dc.contributor.authorBeissert, Tim
dc.date.accessioned2018-09-15T11:43:01Z
dc.date.available2018-09-15T11:43:01Z
dc.date.issued2011-12-30
dc.description.abstractThe BCR/ABL fusion protein is the hallmark of Philadelphia Chromosome positive (Ph+) leukemia. The constitutive activation of the ABL-kinase in BCR/ABL cells induces the leukemic phenotype. Targeted inhibition of BCR/ABL by small molecule inhibitors reverses the transformation potential of BCR/ABL. Recently, we definitively proved that targeting the tetramerization of BCR/ABL mediated by the N-terminal coiled-coil domain (CC) using competitive peptides, representing the helix-2 of the CC, represents a valid therapeutic approach for treating Ph+ leukemia. To further develop competitive peptides for targeting BCR/ABL, we created a membrane permeable helix-2 peptide (MPH-2) by fusing the helix-2 peptide with a peptide transduction tag. In this study, we report that the MPH-2: (i) interacted with BCR/ABL in vivo; (ii) efficiently inhibited the autophosphorylation of BCR/ABL; (iii) suppressed the growth and viability of Ph+ leukemic cells; and (iv) was efficiently transduced into mononuclear cells (MNC) in an in vivo mouse model.en_US
dc.description.sponsorshipThis project was supported by a grant from the Deutsche Forschungsgemeinschaft to M.R., Y.N., J.M., and A.G. (DFG-RU 728/3-2). M.R. is further funded by grants from Deutsche Krebshilfe e.V. (DKH-107063 and DKH-107741), Deutsche José Carreras Leukämie-Stiftung e.V. (DJCLS - R 07/27f), and the Alfred und Angelika Gutermuth Foundation.en_US
dc.identifier.issn1874-2769
dc.identifier.urihttps://dspace.alquds.edu/handle/20.500.12213/902
dc.language.isoen_USen_US
dc.publisherBentham Science Publishersen_US
dc.subjectPhiladelphia Chromosome-positive leukemiaen_US
dc.subjectBCR/ABLen_US
dc.subjectmolecular targetingen_US
dc.subjectcompetitive peptideen_US
dc.subjectoligomerizationen_US
dc.titleTargeting the Oligomerization of BCR/ABL by Membrane Permeable Competitive Peptides Inhibits the Proliferation of Philadelphia Chromosome Positive Leukemic Cellsen_US
dc.typeArticleen_US
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