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Disclosure/Disclaimer

Disclosure/Disclaimer. The Molecular Basis of Hematological Malignancies slide presentation is not an independent educational program, and no CME credits will be provided .

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  1. Disclosure/Disclaimer • The Molecular Basis of Hematological Malignancies slide presentation is not an independent educational program, and no CME credits will be provided. • This program is not intended to promote any cancer agent or class approved by the FDA/EMA or currently under clinical development. • The contents of this slide presentation are owned solely by Genentech; any unauthorized uses are prohibited. • This program is presented on behalf of Genentech and the information presented is consistent with FDA guidelines. • The following slides are selected samples from a complete presentation. They are for educational purposes only. BIO0002078200 1

  2. DLBCL (ABC type) Primary mediastinal B-cell lymphoma B-CLL Marginal zone MALT lymphomaNodal marginal-zone lymphoma Multiple myeloma Germinal center Mantle zone B-CLL (unmutated V gene) Mantle-cell lymphoma B-CLL (unmutated V-region genes) Follicular lymphoma DLBCL (GC type) Burkitt’s lymphoma Classical Hodgkin’s lymphoma Cellular origin of B-cell malignancies Memory B cell GC B cell Naïve B cell Apoptosis B-CLL=B-cell chronic lymphocytic leukemia; DLBCL=diffuse large B-cell lymphoma; MALT=mucosa-associated lymphoid tissue. B-cell differentiation step. Proposed malignancy from normal counterpart. 2 Adapted by permission from Küppers. Nat Rev Cancer. 2005;5:251-262.

  3. AKT Ras PI3K PDK1 Syk Lyn PKC Raf BTK NFκB mTOR MEK MAPK MAPK BCR signaling is central to the pathogenesis of lymphoma Notes Ligand-activated receptors B-cell receptor (BCR) signaling drives many pathways that lead to activation of targeted genes within the nucleus, resulting in lymphomagenesis. Reference: Jumaa H, Hendriks RW, Reth M. B cell signaling and tumorigenesis. Annu Rev Immunol. 2005;23:415-445. Apoptosis Survival Cell-cyclecontrol Angiogenesis Proliferation The Cancer Genome Atlas (TCGA). The National Cancer Institute. 2007. http://cancergenome.nih.gov/media/images.asp. Accessed July 18, 2008. Jumaa et al. Ann Rev Immunol. 2005;23:415-445. 3

  4. Apoptosis Cellularstress Apoptosis is an emerging therapeutic target in lymphoma Pro-apoptotic ligand Cell-extrinsicpathway Death receptor Cell-intrinsic pathway Caspases Mitochondria 5 Ashkenazi. Nat Rev Cancer. 2002;2:420-430.

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