Genetic and Molecular Epidemiology of Multiple Myeloma

Transcription

1 Genetic and Molecular Epidemiology of Multiple Myeloma

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3 Suzanne Lentzsch Editor Genetic and Molecular Epidemiology of Multiple Myeloma

4 Editor Suzanne Lentzsch College of Physicians and Surgeons Multiple Myeloma and Amyloidosis Service Columbia University New York, NY, USA ISBN ISBN (ebook) DOI / Springer New York Heidelberg Dordrecht London Library of Congress Control Number: Springer Science+Business Media New York 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, speci fi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on micro fi lms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied speci fi cally for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a speci fi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (

5 Preface Multiple myeloma is the second most common hematologic malignancy currently effecting approximately 50,000 people in the United States. The disease is characterized by the occurrence of osteolytic bone lesions, renal disease, and immunode fi ciency. Unfortunately, this devastating disease is still incurable. The development of multiple myeloma is a complex multistep process involving both early and late genetic changes affecting the tumor cell itself but also the bone marrow microenvironment. In the last decade, signi fi cant advances have been made in our understanding of the pathogenesis of multiple myeloma including discovery of abnormal gene expression pro fi les, cytogenetic rearrangements, aberrant intra- and intercellular signaling, and cell survival pathways. This enhanced insight into the molecular pathobiology of multiple myeloma has allowed the development of new targeted therapies which have already resulted in palpable improvement of MM treatment options. This book is written by a group of international experts and targets translational and basic researchers to provide insight into the newest breakthroughs from basic pathogenesis to clinical aspects of multiple myeloma. Furthermore, we have attempted to provide a comprehensive overview of the genetic and molecular epidemiology of multiple myeloma in order to get more re fi ned and conclusive understanding of this disease. Areas which are covered include notch signaling as a new target for multiple myeloma and the characterization of different myeloma entities by genomics and proteomics. This book further focuses on targeting protein translation as a new treatment for multiple myeloma, cell cycle control of plasma cell differentiation, the role of osteoclasts and osteoblasts in the pathogenesis of multiple myeloma, as well as a molecular interaction of multiple myeloma with a microenvironment. We therefore hope that this book will provide the reader with a full understanding of where multiple myeloma research stands today and where it is heading. New York, NY, USA Suzanne Lentzsch v

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7 Contents Genetics of Multiple Myeloma... 1 Steven Schuster, Esteban Braggio, and Rafael Fonseca Gene Expression Signature in MGUS and Multiple Myeloma Christoph J. Heuck, Sarah K. Johnson, Qing Zhang, and John D. Shaughnessy Jr. Cap-Dependent Protein Translation Initiation in Multiple Myeloma: An Attractive Target for Therapy Shirong Li, Jing Fu, and Suzanne Lentzsch IRES-Dependent, Cap-Independent Translation in Multiple Myeloma Joseph Gera and Alan Lichtenstein The Role of Notch Signaling in Multiple Myeloma Dehui Xu, Jinsong Hu, Elke De Bruyne, Eline Menu, Karin Vanderkerken, and Els Van Valckenborgh Role of Bone Disease in the Pathogenesis of Multiple Myeloma G. David Roodman Index vii

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