دورية أكاديمية
أعرض في EDS

Reciprocal t(9;22) ABL/BCR fusion proteins: leukemogenic potential and effects on B cell commitment.

التفاصيل البيبلوغرافية
العنوان: Reciprocal t(9;22) ABL/BCR fusion proteins: leukemogenic potential and effects on B cell commitment.
المؤلفون: Xiaomin Zheng, Claudia Oancea, Reinhard Henschler, Malcolm A S Moore, Martin Ruthardt
المصدر: PLoS ONE, Vol 4, Iss 10, p e7661 (2009)
بيانات النشر: Public Library of Science (PLoS), 2009.
سنة النشر: 2009
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: BACKGROUND:t(9;22) is a balanced translocation, and the chromosome 22 breakpoints (Philadelphia chromosome--Ph+) determine formation of different fusion genes that are associated with either Ph+ acute lymphatic leukemia (Ph+ ALL) or chronic myeloid leukemia (CML). The "minor" breakpoint in Ph+ ALL encodes p185(BCR/ABL) from der22 and p96(ABL/BCR) from der9. The "major" breakpoint in CML encodes p210(BCR/ABL) and p40(ABL/BCR). Herein, we investigated the leukemogenic potential of the der9-associated p96(ABL/BCR) and p40(ABL/BCR) fusion proteins and their roles in the lineage commitment of hematopoietic stem cells in comparison to BCR/ABL. METHODOLOGY:All t(9;22) derived proteins were retrovirally expressed in murine hematopoietic stem cells (SL cells) and human umbilical cord blood cells (UCBC). Stem cell potential was determined by replating efficiency, colony forming--spleen and competitive repopulating assays. The leukemic potential of the ABL/BCR fusion proteins was assessed by in a transduction/transplantation model. Effects on the lineage commitment and differentiation were investigated by culturing the cells under conditions driving either myeloid or lymphoid commitment. Expression of key factors of the B-cell differentiation and components of the preB-cell receptor were determined by qRT-PCR. PRINCIPAL FINDINGS:Both p96(ABL/BCR) and p40(ABL/BCR) increased proliferation of early progenitors and the short term stem cell capacity of SL-cells and exhibited own leukemogenic potential. Interestingly, BCR/ABL gave origin exclusively to a myeloid phenotype independently from the culture conditions whereas p96(ABL/BCR) and to a minor extent p40(ABL/BCR) forced the B-cell commitment of SL-cells and UCBC. CONCLUSIONS/SIGNIFICANCE:Our here presented data establish the reciprocal ABL/BCR fusion proteins as second oncogenes encoded by the t(9;22) in addition to BCR/ABL and suggest that ABL/BCR contribute to the determination of the leukemic phenotype through their influence on the lineage commitment.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: http://europepmc.org/articles/PMC2764858?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0007661
URL الوصول: https://doaj.org/article/7786b50bf61240549ce8b95f23bfd62c
رقم الأكسشن: edsdoj.7786b50bf61240549ce8b95f23bfd62c
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0007661