B-cell Signaling

  • NHL is a diverse group of hematologic cancers composed of several subtypes characterized by the cell of origin1,2
  • 85% of NHL is of B-cell origin1
Adapted from Küppers R et al. Nat Rev Cancer. 2005;5:251-260.3
Aggressive Indolent Denotes B-cell differentiation steps Assigns lymphomas to their
proposed normal counterpart

PI3K Signaling Pathways in B-cell Malignancies

  • The phosphatidylinositol-3-kinase (PI3K) pathway is one of the 2 most frequently activated pathways in human cancer.4 This pathway has been shown to play key roles in cell survival, proliferation, and differentation5
  • PI3K is activated downstream of the B-cell receptor (BCR), as well as many other receptors found on B-cells6
  • There are 4 distinct catalytic isoforms of PI3K, which have overlapping functions.6 PI3K class I isoforms include PI3K-alpha(α), -beta(β), -gamma(γ), and -delta(δ)5
  • Signaling from the BCR is known to promote malignant B-cell proliferation and survival6-8
  • In some B-cell malignancies, expression of certain PI3K isoforms is increased upon relapse and may contribute to tumor escape mechanisms6,9-11
AKT=protein kinase B; BTK=Bruton tyrosine kinase; DLBCL=diffuse large B-cell lymphoma; FL=follicular lymphoma; MZL=marginal zone lymphoma (including MALT [mucosa-associated lymphoid tissue], nodal, and splenic lymphomas); CLL=chronic lymphocytic leukemia; SLL=small lymphocytic lymphoma; MCL=mantle cell lymphoma; MZL=marginal zone lymphoma; PIP3=phosphatidylinositol (3,4,5)-trisphosphate; TLRs=toll-like receptors; WM/LPL=Waldenström’s macroglobulinemia/lymphoplasmacytic lymphoma.
References:

1. American Cancer Society. About non-Hodgkin lymphoma. 2016. 2. The Non-Hodgkin's Lymphoma Classification Project. Blood. 1997;89(11):3909-3918. 3. Küppers A. Nat Rev Cancer. 2005;5(4):251-262. 4. Liu N, Scott WJ, Hägebarth A, et al. Poster presented at: 103rd AACR Annual Meeting; March 31-April 4 2012; Chicago, IL. Poster 2799. 5. Liu P, Cheng H, Roberts TM, Zhao JJ. Nat Rev Drug Discov. 2009;8(8):627-644. 6. Fruman DA, Cantley LC. N Engl J Med. 2014;370(11):1061-1062. 7. Lannutti BJ, Meadows SA, Herman SE, et al. Blood. 2011;117(2):591-594. 8. Tzenaki N, Papakonstanti EA. Front Oncol. 2013;3:40. doi:10.3389/fonc.2013.00040. 9. Psyrri A, Papageorgiou S, Liakata E, et al. Clin Cancer Res. 2009;15(18):5724-5732. 10. Brana I, Siu LL. BMC Med. 2012;10:161. doi:10.1186/1741-7015-10-161. 11. Iyengar S, Clear A, Bödör C, et al. Blood. 2013;121(12):2274-2284. 12. Rommel C, Camps M, Ji H. Nat Rev Immunol. 2007;7(3):191-201. 13. Vanhaesbroeck B, Guillermet-Guibert J, Graupera M, Bilanges B. Nat Rev Mol Cell Biol. 2010;11(15):329-341. 14. Arita A, McFarland DC, Myklebust JH, et al. Future Oncol. 2013;9(10):1549-1571. 15. Pfeifer M, Grau M, Lenze D, et al. Proc Natl Acad Sci USA. 2013;110(30):12420-12425.