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Vol. 119, No. 4, 2008
Issue release date: July 2008
Section title: Molecular Drug Targets in Myeloproliferative Neoplasms
Acta Haematol 2008;119:194–198
(DOI:10.1159/000140630)

KIT and Mastocytosis

Lim K.-H. · Pardanani A. · Tefferi A.
Division of Hematology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minn., USA

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Article / Publication Details

First-Page Preview
Abstract of Molecular Drug Targets in Myeloproliferative Neoplasms

Published online: 6/20/2008

Number of Print Pages: 5
Number of Figures: 0
Number of Tables: 0

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: http://www.karger.com/AHA

Abstract

KIT is a receptor tyrosine kinase that is functionally relevant for hematopoiesis, mast cell development and function, gametogenesis and melanogenesis. Normal KIT signaling requires binding to stem cell factor, and PI3K-Akt is one of the putative effector pathways. In humans, germline loss-of-function KIT mutations have been associated with piebaldism – an autosomal dominant condition characterized by depigmented patches of skin and hair. Gain-of-function KIT mutations are usually acquired and have been associated with myeloid malignancies including core binding factor acute myeloid leukemia and systemic mastocytosis (SM), germ cell tumors, gastrointestinal stromal tumors and sinonasal T cell lymphomas. KITD816V is the most prevalent KIT mutation in mast cell disease and occurs in more than 90% of the cases that fulfill the World Health Organization diagnostic criteria for SM. However, its precise pathogenetic contribution is not well understood. In clinical practice, SM is considered either indolent or aggressive depending on the respective absence or presence of symptomatic target organ dysfunction aside from skin disease. In general, conventional therapy for SM is suboptimal, and efforts are under way to develop and employ small molecule drugs that target mutant KIT.


  

Author Contacts

Ayalew Tefferi
Division of Hematology, Department of Internal Medicine
Mayo Clinic College of Medicine, 200 First Street SW
Rochester, MN 55905 (USA)
Tel. +1 507 284 3159, Fax +1 507 266 4972, E-Mail tefferi.ayalew@mayo.edu

  

Article Information

Published online: June 20, 2008
Number of Print Pages : 5
Number of Figures : 0, Number of Tables : 0, Number of References : 66

  

Publication Details

Acta Haematologica

Vol. 119, No. 4, Year 2008 (Cover Date: July 2008)

Journal Editor: Ben-Bassat I. (Qiryat-Ono)
ISSN: 0001–5792 (Print), eISSN: 1421–9662 (Online)

For additional information: http://www.karger.com/AHA


Article / Publication Details

First-Page Preview
Abstract of Molecular Drug Targets in Myeloproliferative Neoplasms

Published online: 6/20/2008

Number of Print Pages: 5
Number of Figures: 0
Number of Tables: 0

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: http://www.karger.com/AHA


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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