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  1. OMICS Group OMICS Group International through its Open Access Initiative is committed to make genuine and reliable contributions to the scientific community. OMICS Group hosts over 400 leading-edge peer reviewed Open Access Journals and organizes over 300 International Conferences annually all over the world. OMICS Publishing Group journals have over 3 million readers and the fame and success of the same can be attributed to the strong editorial board which contains over 30000 eminent personalities that ensure a rapid, quality and quick review process. OMICS Group signed an agreement with more than 1000 International Societies to make healthcare information Open Access. Contact us at: contact.omics@omicsonline.org

  2. Biomarker and Therapeutic Target in Hematologic Malignancy Ken H. Young, MD PhD The University of Texas MD Anderson Cancer Center Houston, Texas Tel: 1-713-745-2598 Email: khyoung@mdanderson.org

  3. Regulation of TP53 at different biological levels

  4. p53 functions through TA and TIA Apoptosis genes Cell cycle arrest Many other genes c-MYC DNA repair MDM2 P Transcriptional Activities p53 transcription-dependent activities (TA)  cell cycle arrest, DNA repair, senescence, apoptosis, and autophagy p53 transcription-independent activities (TIA)  apoptosis and autophagy

  5. p53 functions: cell cycle arrest, DNA repair, apoptosis, senescence, and autophagy Xu-Monette ZY and Young KH. Blood. 2012

  6. TP53 and p53 structure Xu-Monette ZY and Young KH. Blood. 2012

  7. TP53 and p53 structure

  8. p53 transcription-dependent activities in lymphocytes

  9. p53- regulated miRNA genes in lymphocytes ON p53 Transactivation microRNAs: miR-15a, miR-16-1, miR-34a, miR-34b, miR-34c Total 11 microRNAs target TP53 gene: miR-25, miR-30d, miR-125b, miR-504, miR-380-5p, miR-1285, miR-92a, miR-141, miR-200a, miR-15, miR-16

  10. Apoptotic regulation in lymphoma

  11. Posttranslational dysregulation of p53 p53 stability/degradation

  12. p53 MDM2 P53/MDM2 levels A B C Time MDM2 overexpression A D 22% patients MDM2, 0% Number of patients MDM2, 10% Percentage of tumor cells positive for MDM2 expression by IHC B Number of patients 19% patients MDM2, 40% Percentage of tumor cells positive for p53 expression by IHC p53 C MDM2, 100% MDM2

  13. Impact of MDM2 and p53 expression on survival in DLBCL patients with WT- or MUT-p53 MDM2 p53 A B D C F E Months Months

  14. Differentially Expressed Genes in MDM2+ vs MDM2– DLBCLs with MUT-p53

  15. Downstream dysregulation of the TP53 pathway by PI3K/Akt and NF-κB pathways

  16. Therapeutic modulation of the TP53 pathway Xu-Monette ZY and Young KH. Blood. 2012 and 2013

  17. DLBCL Variants, Subgroups, Subtypes, and Other Entities • Common Variants: Centroblastic, immunoblastic, anaplastic • Rare Variants or morphologic types: Myxoid, spindle, fibrillary, signet ring cell, rosette, alveolar, admixed eosinophils, microvillous, admixed crystal-storing histiocytes, intrasinusoidal Morphologic Variants • CD5-positive de novo DLBCL • Germinal center B-cell like • Non-germinal center B-cell like Immunophenotypic Subgroups Molecular Subgroups • Germinal center B-cell like (GCB) • Activated B-cell like (ABC) • T-cell/histiocyte-rich •Primary DLBCL of the CNS •Primary cutaneous DLBCL, leg type •EBV-positive DLBCL of the elderly DLBCL, Subtypes • Primary mediastinal (thymic) large B-cell lymphoma • Intravascular large B-cell lymphoma • DLBCL associated with chronic inflammation • Lymphomatoid granulomatosis •ALK-positive large B-cell lymphoma •Plasmablastic lymphoma •Large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease •Primary effusion lymphoma •CD30-positive de novo large B-cell lymphoma* DLBCL, Other distinct entities

  18. Young KH, et al Neoplastic Hematopathology 2014

  19. Molecular Subgroups Defined by Gene Expression Profiling Visco C and Young KH, et al Leukemia 2012

  20. Immunostain Classification in R-CHOP DLBCL Young KH, et al Neoplastic Hematopathology 2014 Visco C and Young KH, et al Leukemia 2012

  21. Concordance of GEP and IHC for DLBCL Classification - 93% Concordance Visco C and Young KH, et al Leukemia 2012 Young KH, et al Neoplastic Hematopathology 2014

  22. Questions for Lymphoma Study Related to Clinical Management • The DLBCL patients who receive current standard care • Prognostic biomarker and model • Mechanism of ABC molecular subtypes – BCR pathway • Borderline and Gray-zone cases between DLBCL and BL and HL • Stromal signatures in DLBCL – microenvironment • Uniques subtypes (CD30+, CD5+, EBV+, CD138+, Myc, DHL)

  23. ChemotherapyRelated Journals • Journal of Chemotherapy Open Access • Journal of Cancer science and therapy • Journal of Carcinogenesis & Mutagenesis

  24. Chemotherapy Related Conferences • 4th World Congress on Cancer Science and Therapy • World Congress on Pharmacology

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