A Mayado1,2,3,4, C Teodosio5, N Dasilva-Freire1,2,3,4, M Jara-Acevedo4,6, A C Garcia-Montero1,2,3,4, I Álvarez-Twose4,7, L Sánchez-Muñoz4,7, A Matito4,7, C Caldas1,2,3,4, J I Muñoz-González1,2,3,4, A Henriques4,7, J I Sánchez-Gallego1,2,3,4, L Escribano1,2,3,4, A Orfao1,2,3,4. 1. Cancer Research Centre (IBMCC USAL-CSIC), Cytometry Service (NUCLEUS) and Department of Medicine, University of Salamanca, Salamanca, Spain. 2. Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain. 3. Biomedical Research Networking Centre Consortium-CIBER-CIBERONC of the Institute of Health Carlos III, Madrid, Spain. 4. Spanish Network on Mastocytosis (REMA), Toledo, Salamanca, Spain. 5. Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. 6. Sequencing DNA Service (NUCLEUS), University of Salamanca, Salamanca, Spain. 7. Instituto de Estudios de Mastocitosis de Castilla La Mancha (CLMast), Hospital Virgen del Valle, Toledo, Spain.
Abstract
BACKGROUND: Recent studies show that most systemic mastocytosis (SM) patients, including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs-), carry the KIT D816V mutation in PB leukocytes. We investigated the potential association between the degree of involvement of BM hematopoiesis by the KIT D816V mutation and the distribution of different maturation-associated compartments of bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic precursors (HPC) in ISM and identified the specific PB cell compartments that carry this mutation. METHODS: The distribution of different maturation-associated subsets of BM and PB CD34+ HPC from 64 newly diagnosed (KIT-mutated) ISM patients and 14 healthy controls was analyzed by flow cytometry. In 18 patients, distinct FACS-purified PB cell compartments were also investigated for the KIT mutation. RESULTS: ISM patients showed higher percentages of both BM and PB MC-committed CD34+ HPC vs controls, particularly among ISM cases with MC-restricted KIT mutation (ISMMC ); this was associated with progressive blockade of maturation of CD34+ HPC to the neutrophil lineage from ISMMC to multilineage KIT-mutated cases (ISMML ). Regarding the frequency of KIT-mutated cases and cell populations in PB, variable patterns were observed, the percentage of KIT-mutated PB CD34+ HPC, eosinophils, neutrophils, monocytes and T cells increasing from ISMs-MC and ISMs+MC to ISMML patients. CONCLUSION: The presence of the KIT D816V mutation in PB of ISM patients is associated with (early) involvement of circulating CD34+ HPC and multiple myeloid cell subpopulations, KIT-mutated PB CD34+ HPC potentially contributing to early dissemination of the disease.
BACKGROUND: Recent studies show that most systemic mastocytosis (SM) patients, including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs-), carry the KITD816V mutation in PB leukocytes. We investigated the potential association between the degree of involvement of BM hematopoiesis by the KITD816V mutation and the distribution of different maturation-associated compartments of bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic precursors (HPC) in ISM and identified the specific PB cell compartments that carry this mutation. METHODS: The distribution of different maturation-associated subsets of BM and PB CD34+ HPC from 64 newly diagnosed (KIT-mutated) ISM patients and 14 healthy controls was analyzed by flow cytometry. In 18 patients, distinct FACS-purified PB cell compartments were also investigated for the KIT mutation. RESULTS: ISM patients showed higher percentages of both BM and PB MC-committed CD34+ HPC vs controls, particularly among ISM cases with MC-restricted KIT mutation (ISMMC ); this was associated with progressive blockade of maturation of CD34+ HPC to the neutrophil lineage from ISMMC to multilineage KIT-mutated cases (ISMML ). Regarding the frequency of KIT-mutated cases and cell populations in PB, variable patterns were observed, the percentage of KIT-mutated PB CD34+ HPC, eosinophils, neutrophils, monocytes and T cells increasing from ISMs-MC and ISMs+MC to ISMML patients. CONCLUSION: The presence of the KITD816V mutation in PB of ISM patients is associated with (early) involvement of circulating CD34+ HPC and multiple myeloid cell subpopulations, KIT-mutated PB CD34+ HPC potentially contributing to early dissemination of the disease.
Authors: Hanneke C Kluin-Nelemans; Andreas Reiter; Anja Illerhaus; Bjorn van Anrooij; Karin Hartmann; Lambertus F R Span; Aleksandra Gorska; Marek Niedoszytko; Magdalena Lange; Luigi Scaffidi; Roberta Zanotti; Patrizia Bonadonna; Cecelia Perkins; Chiara Elena; Luca Malcovati; Khalid Shoumariyeh; Nikolas von Bubnoff; Roberta Parente; Massimo Triggiani; Juliana Schwaab; Mohamad Jawhar; Francesca Caroppo; Anna Belloni Fortina; Knut Brockow; Alexander Zink; David Fuchs; Alex Kilbertus; Akif Selim Yavuz; Michael Doubek; Mattias Mattsson; Hans Hagglund; Jens Panse; Vito Sabato; Elisabeth Aberer; Dietger Niederwieser; Christine Breynaert; Judit Várkonyi; Vanessa Kennedy; Olivier Lortholary; Thilo Jakob; Olivier Hermine; Julien Rossignol; Michel Arock; Jason Gotlib; Peter Valent; Wolfgang R Sperr Journal: Leukemia Date: 2019-11-18 Impact factor: 11.528
Authors: Oscar González-López; Javier I Muñoz-González; Alberto Orfao; Iván Álvarez-Twose; Andrés C García-Montero Journal: Cancers (Basel) Date: 2022-05-18 Impact factor: 6.575
Authors: Georg Greiner; Michael Gurbisz; Franz Ratzinger; Nadine Witzeneder; Svenja Verena Class; Gregor Eisenwort; Ingrid Simonitsch-Klupp; Harald Esterbauer; Matthias Mayerhofer; Leonhard Müllauer; Wolfgang R Sperr; Peter Valent; Gregor Hoermann Journal: Haematologica Date: 2020-01-31 Impact factor: 9.941