دورية أكاديمية
The functional interplay between the t(9;22)-associated fusion proteins BCR/ABL and ABL/BCR in Philadelphia chromosome-positive acute lymphatic leukemia.
| العنوان: | The functional interplay between the t(9;22)-associated fusion proteins BCR/ABL and ABL/BCR in Philadelphia chromosome-positive acute lymphatic leukemia. |
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| المؤلفون: | Anahita Rafiei, Afsar Ali Mian, Claudia Döring, Anna Metodieva, Claudia Oancea, Frederic B Thalheimer, Martin Leo Hansmann, Oliver Gerhard Ottmann, Martin Ruthardt |
| المصدر: | PLoS Genetics, Vol 11, Iss 4, p e1005144 (2015) |
| بيانات النشر: | Public Library of Science (PLoS), 2015. |
| سنة النشر: | 2015 |
| المجموعة: | LCC:Genetics |
| مصطلحات موضوعية: | Genetics, QH426-470 |
| الوصف: | The hallmark of Philadelphia chromosome positive (Ph(+)) leukemia is the BCR/ABL kinase, which is successfully targeted by selective ATP competitors. However, inhibition of BCR/ABL alone is unable to eradicate Ph(+) leukemia. The t(9;22) is a reciprocal translocation which encodes not only for the der22 (Philadelphia chromosome) related BCR/ABL, but also for der9 related ABL/BCR fusion proteins, which can be detected in 65% of patients with chronic myeloid leukemia (CML) and 100% of patients with Ph+ acute lymphatic leukemia (ALL). ABL/BCRs are oncogenes able to influence the lineage commitment of hematopoietic progenitors. Aim of this study was to further disclose the role of p96(ABL/BCR) for the pathogenesis of Ph(+) ALL. The co-expression of p96(ABL/BCR) enhanced the kinase activity and as a consequence, the transformation potential of p185(BCR/ABL). Targeting p96(ABL/BCR) by RNAi inhibited growth of Ph(+) ALL cell lines and Ph(+) ALL patient-derived long-term cultures (PD-LTCs). Our in vitro and in vivo stem cell studies further revealed a functional hierarchy of p96(ABL/BCR) and p185(BCR/AB)L in hematopoietic stem cells. Co-expression of p96(ABL/BCR) abolished the capacity of p185(BCR/ABL) to induce a CML-like disease and led to the induction of ALL. Taken together our here presented data reveal an important role of p96(ABL/BCR) for the pathogenesis of Ph(+) ALL. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7390 1553-7404 |
| Relation: | http://europepmc.org/articles/PMC4412790?pdf=render; https://doaj.org/toc/1553-7390; https://doaj.org/toc/1553-7404 |
| DOI: | 10.1371/journal.pgen.1005144 |
| URL الوصول: | https://doaj.org/article/e656123223284eafa41f1d7b430b3911 |
| رقم الأكسشن: | edsdoj.656123223284eafa41f1d7b430b3911 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537390 15537404 |
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| DOI: | 10.1371/journal.pgen.1005144 |