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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The t(9;22) is a reciprocal translocation, which causes chronic myeloid leukemia (CML) and a subset of high risk acute lymphatic leukemia (ALL). The derivative chromosome 22 is the so called Philadelphia chromosome (Ph) which encodes the BCR/ABL kinase. Targeting BCR/ABL by selective ATP competitors, such as imatinib or nilotinib, is a well validated therapeutic concept, but unable to definitively eradicate the disease. Little is known about the role of the fusion protein encoded by the reciprocal derivative chromosome 9, the ABL/BCR. In models of Ph+ ALL we show that the functional interplay between ABL/BCR and BCR/ABL not only increases the transformation potential of BCR/ABL but is also indispensable for the growth and survival of Ph+ ALL leukemic cells. The presence of ABL/BCR changed the phenotype of the leukemia most likely due to its capacity to influence the stem cell population as shown by our in vivo data. Taken together our here presented data reveal an important role of p96ABL/BCR for the pathogenesis of Ph+ ALL.

Vyšlo v časopise: The Functional Interplay Between the t(9;22)-Associated Fusion Proteins BCR/ABL and ABL/BCR in Philadelphia Chromosome-Positive Acute Lymphatic Leukemia. PLoS Genet 11(4): e32767. doi:10.1371/journal.pgen.1005144
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005144

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