1 / 18

Multiple Myeloma

Multiple Myeloma. Plasma cell malignancy About 300 new cases in Norway each year Incurable Mean survival after diagnosis: 3-4 years Malignant plasma cells found in the bone marrow Osteolytic lesions common complication. Chromosomal-translocations associated with human cancer.

magee
Download Presentation

Multiple Myeloma

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Multiple Myeloma • Plasma cell malignancy • About 300 new cases in Norway each year • Incurable • Mean survival after diagnosis: 3-4 years • Malignant plasma cells found in the bone marrow • Osteolytic lesions common complication

  2. Chromosomal-translocations associated with human cancer • Uncommon in cancers derived from epithelial tissues (which comprises >80% of • human tumores) • Found in tumours derived from mesenchymal tissues • Often in haematological cancers as a by-product of natural DNA recombination • that take place to generate antigen-receptors • In B-cell tumours (ALL, CLL, Lymfoma, Multiple Myeloma) • - translocations involving Ig heavy chain genes (14q32) • In T-cell tumours (ALL, Lymfom) • - Often translocations involving the TCR delta chain (14q11)

  3. Differentiation and maturation in the B-cell lineage

  4. Lymphoplasmacyte WALDENSTROM’S IgM Germinal Center Lymph node SOMATIC Lymphoblast HYPERMUTATION BURKITT’S LYMPHOMA Plasmablast FOLLICULAR LYMPHOMA Virgin B cell CLL Bone Marrow MULTIPLE MYELOMA ALL Plasma cell G,A,E Pre-B cell Overview of cancers derived from cells at various stages in the the B-cell lineage

  5. Translocations involving the IgH locus (14q23) in multiple myeloma: Multiple myeloma is cancer due to transformation of plasma cells (antibody- producing cells). In about half of these tumours translocations involving the IgH locus as one partner is found. These translocations results in cellular genes involved growth control come under control of the Ig enhancer, resulting in aberrant expression of these genes. From L. Bergsagel 2001 http://myeloma

  6. Extra-medullary Myeloma Intra-medullary Myeloma Normal Plasmablast MGUS IgH translocation karyotypic instability 13q12-14 monosomy/deletion c-myc translocation activating mutations N, K - ras FGFR3 p53 mutation Progressive genetic events also in multiple myeloma

  7. Bone marrow aspirate form a multiple myeloma patient

  8. Syndecan-1 Heparan sulfate proteoglycan Transmembrane Shed

  9. sSyndecan-1 in sera of patients with multiple myeloma Seidel et al. Blood 2000 Apr 1;95(7):2197

  10. HGF in sera of patients with multiple myeloma Seidel et al. Blood. 1998 Feb 1;91(3):806-12.

  11. Binding of HGF to JJN-3 myeloma cells with or without sSyndecan-1 or heparin wash

  12. The presentation of HGF TransWell Co-culture Oligomerization

  13. 250 200 150 IL-11 (% of control) 100 50 0 1 1 1 1 0 0 1 1 1 HGF (ng/ml) 0 1.5 0.15 0 1.5 Syndecan-1 (mg/ml) 1.5 0.015 0.5 3.0 + aHGF Soluble Syndecan-1 potentiates HGF

  14. sSyndecan-1 i serum hos myelomatosepasienter Seidel et al. Blood 2000 Apr 1;95(7):2197

  15. Fig. 1 The proposed functions of syndecan extracellular domain shedding M. D. Bass et al., Sci. Signal. 2, pe18 (2009) Published by AAAS

  16. Ralph D Sanderson University of Alabama, Birmingham ”Regulation of myeloma progression by the syndecan-1/heparanase axis; a vulnerable target for therapy” MTA, 11.30 Friday November 13., 2009

More Related