any effects on SYK phosphorylation. In addition AQX-435 was able to augment inhibition of
the BCR pathway by ibrutinib. AQX-435 induced apoptosis of CLL cells in a caspase dependent
manner in a preferential manner compared to normal B cells. Finally in a DLBCL model AQX-
435 synergised with ibrutinib to prevent tumour growth. Whilst AQX-435 would not be used
clinically, it highlight another mechanism of action for inhibiting the BCR signalling pathway in
B cell malignancies that may have therapeutic potential.
References
1. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig V(H) genes are
associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94(6):1848-1854.
2. Damle RN, Wasil T, Fais F, et al. Ig V gene mutation status and CD38 expression as novel
prognostic indicators in chronic lymphocytic leukemia. Blood. 1999;94(6):1840-1847.
3. Aguilar-Hernandez MM, Blunt MD, Dobson R, et al. IL-4 enhances expression and function of
surface IgM in CLL cells. Blood. 2016;127(24):3015-3025.
4. Venetoclax Approved for CLL. Cancer Discov. 2016.
5. Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 with Venetoclax in Relapsed Chronic
Lymphocytic Leukemia. N Engl J Med. 2016;374(4):311-322.
6. Kotschy A, Szlavik Z, Murray J, et al. The MCL1 inhibitor S63845 is tolerable and effective in
diverse cancer models. Nature. 2016;538(7626):477-482.
7. Lemm EA, Valle-Argos B, Smith LD, et al. Preclinical evaluation of a novel SHIP1 phosphatase
activator for inhibition of PI3K signaling in malignant B-cells. Clin Cancer Res. 2019.