No conflicts of interest were declared.
Variable presence of KITD816V in clonal haematological non-mast cell lineage diseases associated with systemic mastocytosis (SM–AHNMD)†
Article first published online: 22 DEC 2009
Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 220, Issue 5, pages 586–595, April 2010
How to Cite
Sotlar, K., Colak, S., Bache, A., Berezowska, S., Krokowski, M., Bültmann, B., Valent, P. and Horny, H.-P. (2010), Variable presence of KITD816V in clonal haematological non-mast cell lineage diseases associated with systemic mastocytosis (SM–AHNMD). J. Pathol., 220: 586–595. doi: 10.1002/path.2677
- Issue published online: 3 MAR 2010
- Article first published online: 22 DEC 2009
- Accepted manuscript online: 22 DEC 2009 12:00AM EST
- Manuscript Accepted: 15 DEC 2009
- Manuscript Revised: 9 DEC 2009
- Manuscript Received: 5 OCT 2009
- Fortüne Förderprogramm der Universität Tübingen. Grant Number: F1461141
- bone marrow;
- tyrosine kinase inhibitors
In a substantial number of patients with systemic mastocytosis (SM), an associated clonal haematological non-mast cell lineage disease (AHNMD) is detectable. Although most of these patients display KIT mutations, especially KITD816V, little is known about their exact frequency and their distribution in AHNMD subtypes. We examined 48 patients with SM–AHNMD for the presence of mutant KIT in the SM and AHNMD components of the disease. Mast cells and AHNMD cells were obtained from immunostained bone marrow sections by laser microdissection and examined by melting point analysis of nested-PCR products. KITD816V was found in AHNMD cells in the vast majority of patients with SM–chronic myelomonocytic leukaemia (CMML, 89%). Unexpectedly, KITD816V was far less frequently detectable in AHNMD cells in patients with SM–myeloproliferative neoplasm (MPN, 20%) and SM–acute myeloid leukaemia (AML, 30%). None of the patients with lymphoproliferative AHNMDs displayed KIT codon 816 mutations in AHNMD cells (0/8). In FIP1L1/PDGFRA-positive chronic eosinophilic leukaemia (CEL), neither the SM nor the CEL component of the disease exhibited the KIT mutation. Our findings demonstrate that KIT codon 816 mutations are variably present in AHNMD cells in patients with SM–AHNMD, depending on the subtype of AHNMD. The high frequency of KITD816V in neoplastic mast cells and leukaemic myelomonocytic cells in SM–CMML may point to a common precursor in these patients, and may have implications for the biology of the disease and the development of KIT-targeting therapies. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.