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Plcg1 signaling in hematopoietic stem cells
Projektbearbeiter:
Patricia Arrreba
Finanzierung:
Haushalt;
Chronic myeloid leukemia is a myeloproliferative neoplasia initiated by the constitutively active fusion-kinase BCR-ABL and characterized by massive proliferation of phenotypically normal myeloid cells. Nowadays, a targeted therapy using inhibitors of BCR-ABL (imatinib) has improved the disease prognosis. However, a resistance from a persistent malignant cell pool impairs its eradication. In our previous work, we were able to demonstrate the important role of phospholipase-C-gamma1 (PLCg1) pathway in leukemia development of CML. We proved an activation of the BCR-ABL dowstream pathway mTOR-p70S6-kinase, controlled by PLCg1 and parallel to the classical signaling pathways. Moreover, PLCg1 pathway might be a potential target in myeloproliferative neoplasias, as we have also demonstrated synergistic inhibition of PLCg1 with the tyrosine kinase inhibitor imatinib. However, before using it as a therapeutic target it is crucial to understand its relevance in development and maintenance of normal hematopoiesis. It has been shown already that a lost of PLCg1 in mouse leads to a disruption of erythropoiesis in early fetal development. Therefore, our goal is to investigate the biological relevance of PLCg1 in normal hematopoiesis by an RNA interference approach, studying the hematopoietic stem cells in a stage of development (fetal liver cells) and maintenance (adult HSC).

Schlagworte

signaling, stem cell
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