January 22, 2019

Dr. Chen Zhao received a four-year VA Merit Award entitled “Synergy of NF‑κB and Notch signaling in B cell lymphomatous transformation and B cell plasticity”. The studies will use genetic mouse models in combination with human leukemia samples to investigate 1) whether concurrent activation of NF‑κB and Notch signaling in committed B cells is sufficient to induce lymphomatous transformation; 2) whether NF‑κB/Notch-coactivated B cells are self-renewing and have the potential to convert to myeloid lineage in a permissive microenvironment; 3) whether it is the NF‑κB/Notch-coactivated common progenitor/pre-lymphoma cells that convert to myeloid lineage and whether similar common progenitor cells can be identified in concurrent human lymphoid and myeloid leukemias; 4) whether B-myeloid conversion is through dedifferentiation; 5) the existence of a specific subgroup of CLL with myeloid-biased somatic mutations that has the potential to develop myeloid neoplasm; and 6) the underlying mechanisms for lymphomatous and myeloid transformation. The expected results will not only clarify a number of clinical uncertainties in the field, but also provide new insights on treating lymphomas and those myeloid tumors that converted from lymphomas.