Md Kamrul Hasan, PhD

Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adults. It accounts for more than 20,000 new cases every year in the United States and 37% of all newly detected leukemia cases. CLL is characterized by the accumulation of B cells (a type of white blood cell that express B-cell receptor (BCR)) in the bone marrow and lymphoid tissues (e.g. spleen). DOCK2 is a cytoplasmic protein of hematopoietic cells (blood cells), and can directly activate Rac1/2. Wnt5a is a growth factor found at high levels in the plasma of patients with CLL, and a ligand (have high affinity) of ROR1, which is present on the surface of CLL cells. Recently, we described that Wnt5a can induce ROR1/DOCK2 association, activate Rac1/2 or ERK1/2 and promote leukemia-cell proliferation (increase cell number/growth), and could be inhibited by cirmtuzumab (anti-ROR1 antibody), which is under phase-II clinical trial to treat CLL patients (Hasan et al., Blood, 2018; Leukemia, 2020). Moreover, an FDA approved front line therapy to treat CLL patients such, as ibrutinib (BTK inhibitor) that could inhibit BCR signaling, was unable to block Wnt5a enhanced activation of DOCK2 or ERK1/2, suggesting potential drug resistance in CLL therapy. Here, we will examine the molecular events of activation of DOCK2 or ERK1/2 in CLL. This study will provide better understanding of DOCK2 protein in CLL cells expansion and pathogenesis, and suggest new therapeutic strategies to treat CLL.