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

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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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