KIT mutation and AHN-associated oncogenic profiles in systemic mastocytosis with an associated hematological neoplasm
Year: 2026
Type: article
Study design: Observational Study
Abstract: ABSTRACT: In 5% to 15% of patients with systemic mastocytosis (SM), SM coexists with an associated hematological neoplasm (AHN). Most patients with SM-AHN harbor a KIT mutation, mainly KIT p.D816V, together with other AHN-related genetic alterations; however, limited data exist about the frequency and clinical impact of the coexistence of both types of genetic alterations in the same vs distinct bone marrow (BM) cell compartments. Here, we analyzed 79 patients with SM-AHN classified into patients who (1) displayed distinct unrelated genetic alterations in BM mast cells (MC) and AHN cells (21/79 [27%]); (2) shared the KIT mutation as a first genetic event (24/79 [30%]) involving both BM MC and AHN cells, together with or without AHN-associated alterations restricted to the latter cells; (3) had AHN-associated alterations as a first event (25/79 [32%]) present in both BM MC and AHN cells; and (4) had both alterations involving virtually all SM and AHN cells (9/79 [11%]). Overall, patients with genetically unrelated SM and AHN more frequently showed clinical manifestations associated with SM (ie, anaphylaxis, osteoporosis, and skin lesions) together with prolonged progression-free survival (PFS), whereas those with shared genetic alterations displayed signs of more advanced disease (ie, cytopenias or organomegalies) and shorter PFS and overall survival. Our findings confirm the clinical, genetic, and prognostic heterogeneity of SM-AHN and point to its association with the underlying oncogenic profile of neoplastic MC and AHN cells.
Source: Blood Advances
Authors: Paula Navarro-Navarro, Carlos M. Fernández-Giménez, Andrés C. García-Montero, Iván Álvarez-Twose, Laura Sánchez-Muñoz, Ana Henriques, Alba Pérez-Pons, María González-Tablas, Cristina Teodosio, María González-González, Sergio Matarraz, Antonio López, Paloma Barcena, Enrique Colado, Jordi Esteve, Mª Leonor Senent, Óscar González-López, Manuela Mollejo, Cristina Morales-Cabeza, María Jara-Acevedo, Alberto Orfao
Institutions: Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer, Centro de Investigación Biomédica en Red de Cáncer, Hospital Virgen del Valle, Hospital Universitario Central de Asturias, Josep Carreras Leukaemia Research Institute, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona, Hospital Universitari i Politècnic La Fe, Instituto de Investigación Sanitaria La Fe, Complejo Hospitalario Universitario de Toledo, Hospital Universitario de Toledo
Language: English
Topic: Mast cells and histamine
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,800
OpenAlex ID: W7165045394