Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Jan 28;3(1):4.
doi: 10.1186/2162-3619-3-4.

Ibrutinib for B cell malignancies

Aileen Novero, Pavan M Ravella, Yamei Chen, George Dous, Delong Liu  1
Affiliations

Ibrutinib for B cell malignancies

Aileen Novero et al. Exp Hematol Oncol. .

Abstract

Research over the role of Bruton's agammaglobulinemia tyrosine kinase (BTK) in B-lymphocyte development, differentiation, signaling and survival has led to better understanding of the pathogenesis of B-cell malignancies. Down-regulation of BTK activity is an attractive novel strategy for treating patients with B-cell malignancies. Ibrutinib (PCI-32765), a potent inhibitor of BTK induces impressive responses in B-cell malignancies through irreversible bond with cysteine-481 in the active site of BTK (TH/SH1 domain) and inhibits BTK phosphorylation on Tyr223. This review discussed in details the role of BTK in B-cell signaling, molecular interactions between B cell lymphoma/leukemia cells and their microenvironment. Clinical trials of the novel BTK inhibitor, ibrutinib (PCI-32765), in B cell malignancies were summarized.

PubMed Disclaimer

Figures

Figure 1
Figure 1
A schematic representation of BCR/BTK signaling pathway. The BCR consists of a transmembrane immunoglobulin (Ig) receptor associated with the Ig-alpha (CD79a) and Ig-beta (CD79b) heterodimers. The activation of BTK and PI3 kinase after antigen binding to BCR prompts calcium release, which leads to activation of the signaling cascade. BCR: B cell receptor; BTK: Bruton’s tyrosine kinase.
See this image and copyright information in PMC

References

    1. Akinleye A, Chen Y, Mukhi N, Song Y, Liu D. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol. 2013;6(1):59. doi: 10.1186/1756-8722-6-59. - DOI - PMC - PubMed
    1. Mohamed AJ, Yu L, Backesjo CM, Vargas L, Faryal R, Aints A, Christensson B, Berglof A, Vihinen M, Nore BF. et al.Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunol Rev. 2009;228(1):58–73. doi: 10.1111/j.1600-065X.2008.00741.x. - DOI - PubMed
    1. Pan Z, Scheerens H, Li SJ, Schultz BE, Sprengeler PA, Burrill LC, Mendonca RV, Sweeney MD, Scott KC, Grothaus PG. et al.Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase. Chem Med Chem. 2007;2(1):58–61. doi: 10.1002/cmdc.200600221. - DOI - PubMed
    1. Cheson BD, Plass RR, Rothstein G. Defective opsonization in multiple myeloma. Blood. 1980;55(4):602–606. - PubMed
    1. Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang Y. et al.Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature. 2010;463(7277):88–92. doi: 10.1038/nature08638. - DOI - PMC - PubMed