P. Perez-galan, M. Dreyling, and A. Wiestner, Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era, Blood, vol.117, pp.26-38, 2011.

A. J. Mohamed, L. Yu, C. M. Backesjo, L. Vargas, R. Faryal et al., Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain, Immunol Rev, vol.228, pp.58-73, 2009.

O. C. Bruton and . Agammaglobulinemia, Pediatrics, vol.9, pp.722-730, 1952.

R. M. Young and L. M. Staudt, Targeting pathological B cell receptor signalling in lymphoid malignancies, Nat Rev Drug Discov, vol.12, pp.229-272, 2013.

L. A. Honigberg, A. M. Smith, M. Sirisawad, E. Verner, D. Loury et al., The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is effi cacious in models of autoimmune disease and B-cell malignancy, Proc Natl Acad Sci U S A, vol.107, pp.13075-80, 2010.

M. L. Wang, S. Rule, P. Martin, A. Goy, R. Auer et al., Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma, N Engl J Med, vol.369, pp.507-523, 2013.

J. C. Byrd, R. R. Furman, S. E. Coutre, I. W. Flinn, J. A. Burger et al., Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia, N Engl J Med, vol.369, pp.32-42, 2013.

, Ibrutinib approved for mantle cell lymphoma, Cancer Discov, vol.4, p.1, 2014.

O. Determann, E. Hoster, G. Ott, W. Bernd, H. Loddenkemper et al., Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group, Blood, vol.111, pp.2385-2392, 2008.

D. W. Fry, P. J. Harvey, P. R. Keller, W. L. Elliott, M. Meade et al., Specifi c inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts, Mol Cancer Ther, vol.3, pp.1427-1465, 2004.

J. P. Leonard, A. S. Lacasce, M. R. Smith, A. Noy, L. R. Chirieac et al., Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma, Blood, vol.119, pp.4597-607, 2012.

, Palbociclib Ups PFS in HER2?/ER+ breast cancer, Cancer Discov, vol.4, pp.624-629, 2014.

L. B. Baughn, D. Liberto, M. Wu, K. Toogood, P. L. Louie et al., A novel orally active small molecule potently induces G 1 arrest in primary myeloma cells and prevents tumor growth by specifi c inhibition of cyclin-dependent kinase 4/6, Cancer Res, vol.66, pp.7661-7668, 2006.

X. Huang, D. Liberto, M. Jayabalan, D. Liang, J. Ely et al., Prolonged early G(1) arrest by selective CDK4/CDK6 inhibition sensitizes myeloma cells to cytotoxic killing through cell cycle-coupled loss of IRF4, Blood, vol.120, pp.1095-106, 2012.

E. Menu, J. Garcia, X. Huang, D. Liberto, M. Toogood et al., A novel therapeutic combination using PD 0332991 and bortezomib: study in the 5T33MM myeloma model, Cancer Res, vol.68, pp.5519-5542, 2008.

D. Chiron, P. Martin, D. Liberto, M. Huang, X. Ely et al., Induction of prolonged early G 1 arrest by CDK4/CDK6 inhibition reprograms lymphoma cells for durable PI3Kdelta inhibition through PIK3IP1, Cell Cycle, vol.12, pp.1892-900, 2013.

T. C. Greiner, C. Dasgupta, V. V. Ho, D. D. Weisenburger, L. M. Smith et al., Mutation and genomic deletion status of ataxia telangiectasia mutated (ATM) and p53 confer specifi c gene expression profi les in mantle cell lymphoma, Proc Natl Acad Sci, vol.103, pp.2352-2359, 2006.

B. Meissner, R. Kridel, R. S. Lim, S. Rogic, K. Tse et al., The E3 ubiquitin ligase UBR5 is recurrently mutated in mantle cell lymphoma, Blood, vol.121, pp.3161-3165, 2013.

S. Bea, R. Valdes-mas, A. Navarro, I. Salaverria, D. Martin-garcia et al., Landscape of somatic mutations and clonal evolution in mantle cell lymphoma, Proc Natl Acad Sci U S A, vol.110, pp.18250-18255, 2013.

R. Rahal, M. Frick, R. Romero, J. M. Korn, R. Kridel et al., Pharmacological and genomic profi ling identifi es NF-kappaBtargeted treatment strategies for mantle cell lymphoma, Nat Med, vol.20, pp.87-92, 2014.

J. Zhang, D. Jima, A. B. Moffi-tt, Q. Liu, M. Czader et al., The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells, Blood, vol.123, pp.2988-96, 2014.

A. Yamasaki, S. Menon, S. Yu, J. Barrowman, T. Meerloo et al., mTrs130 is a component of a mammalian TRAPPII complex, a Rab1 GEF that binds to COPI-coated vesicles, Mol Biol Cell, vol.20, pp.4205-4220, 2009.

J. A. Woyach, R. R. Furman, T. M. Liu, H. G. Ozer, M. Zapatka et al., Resistance mechanisms for the Bruton's tyrosine kinase inhibitor ibrutinib, N Engl J Med, vol.370, pp.2286-94, 2014.

B. Vanhaesebroeck, M. J. Welham, K. Kotani, R. Stein, P. H. Warne et al., P110delta, a novel phosphoinositide 3-kinase in leukocytes, Proc Natl Acad Sci U S A, vol.94, pp.4330-4335, 1997.

B. Y. Chang, M. Francesco, D. Rooij, M. F. Magadala, P. Steggerda et al., Egress of CD19+CD5+ cells into peripheral blood following treatment with the BTK inhibitor ibrutinib in mantle cell lymphoma patients, Blood, vol.122, pp.2412-2436, 2013.

Z. Zhu, X. He, C. Johnson, J. Stoops, A. E. Eaker et al., PI3K is negatively regulated by PIK3IP1, a novel p110 interacting protein, Biochem Biophys Res Commun, vol.358, pp.66-72, 2007.

D. A. Fruman, S. B. Snapper, C. M. Yballe, L. Davidson, J. Y. Yu et al., Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alpha, Science, vol.283, pp.393-400, 1999.

L. Srinivasan, Y. Sasaki, D. P. Calado, B. Zhang, J. H. Paik et al., PI3 kinase signals BCR-dependent mature B cell survival, Cell, vol.139, pp.573-86, 2009.

S. E. Herman, A. L. Gordon, A. J. Wagner, N. A. Heerema, W. Zhao et al., American Association for Cancer cancerdiscovery.aacrjournals.org Downloaded from antagonizing intrinsic and extrinsic cellular survival signals, Blood, vol.116, pp.2078-88, 2010.

J. Hoellenriegel, S. A. Meadows, M. Sivina, W. G. Wierda, H. Kantarjian et al., The phosphoinositide 3?-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia, Blood, vol.118, pp.3603-3615, 2011.

B. J. Lannutti, S. A. Meadows, S. E. Herman, A. Kashishian, B. Steiner et al., CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability, Blood, vol.117, pp.591-595, 2011.

N. Liu, B. R. Rowley, C. O. Bull, C. Schneider, A. Haegebarth et al., BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110alpha and p110delta activities in tumor cell lines and xenograft models, Mol Cancer Ther, vol.12, pp.2319-2349, 2013.

A. J. Folkes, K. Ahmadi, W. K. Alderton, A. S. Baker, S. J. Box et al., The identifi cation of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer, J Med Chem, vol.51, pp.5522-5554, 2008.

J. A. Meyer, J. Wang, L. E. Hogan, J. J. Yang, S. Dandekar et al., Relapse-specifi c mutations in NT5C2 in childhood acute lymphoblastic leukemia, Nat Genet, vol.45, pp.290-294, 2013.

S. Bea, I. Salaverria, L. Armengol, M. Pinyol, V. Fernandez et al., Uniparental disomies, homozygous deletions, amplifi cations, and target genes in mantle cell lymphoma revealed by integrative high-resolution whole-genome profi ling, Blood, vol.113, pp.3059-69, 2009.

C. Y. Ying, D. Dominguez-sola, M. Fabi, I. C. Lorenz, S. Hussein et al., MEF2B mutations lead to deregulated expression of the oncogene BCL6 in diffuse large B cell lymphoma, Nat Immunol, vol.14, pp.1084-92, 2013.

S. J. Klempner, A. P. Myers, and L. C. Cantley, What a tangled web we weave: emerging resistance mechanisms to inhibition of the phosphoinositide 3-kinase pathway, Cancer Discov, vol.3, pp.1345-54, 2013.

P. Liu, M. Begley, W. Michowski, H. Inuzuka, M. Ginzberg et al., Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus, Nature, vol.508, pp.541-546, 2014.

M. Takata and T. Kurosaki, A role for Bruton's tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-gamma 2, J Exp Med, vol.184, pp.31-40, 1996.