A10: Investigating the crosstalk between pre-BCR and IL7-R signaling in B-cell precursor acute lymphoblastic leukemia
B cell precursor (BCP) ALL is characterized by abnormal expansion of transformed pro-/pre-B cells. In the previous funding period, we identified a crucial role of the interleukin 7 receptor (IL7R) in BCP-ALL and found that IL7R interacts with the chemokine receptor CXCR4 and with components of the precursor-B cell receptor. In the next funding period, we aim at characterizing the role of IL7R in BCP-ALL development induced by known oncogenes such as BCR-ABL1, the oncogenic fusion kinase in Philadelphia chromosome-positive (Ph+) ALL. We will test whether BCR-ABL1-mediated pro-/pre-B cell transformation requires direct interaction between IL7R and CXCR4. A synergism between the IL7R and the pre-BCR signaling has been postulated to accelerate the proliferation of pre-BCR-positive cells leading to their selective enrichment in the bone marrow. Therefore, we will investigate the crosstalk between IL7R and pre-BCR signaling in order to understand their role in malignant transformation and BCP-ALL development.
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