Targeting the oligomerization of BCR/ABL by membrane permeable competitive peptides inhibits the proliferation of Philadelphia Chromosome positive leukemic cells

Afsar Ali Mian, Marion Schüll, Claudia Oancea, Yousef Najajreh, Jamal Mahajna, Amiram Goldblum, Oliver Gerhard Ottmann, Tim Beissert, Martin Ruthardt*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The 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. This study provides the first evidence that an efficient peptide transduction system facilitates the employment of competitive peptides to target the oligomerization interface of BCR/ABL in vivo.

Original languageAmerican English
Pages (from-to)21-27
Number of pages7
JournalOpen Hematology Journal
Issue number1
StatePublished - 2011


  • Competitive peptide
  • Molecular targeting
  • Oligomerization
  • Philadelphia Chromosome-positive leukemia

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