KIT Mutations and Other Genetic Defects in Mastocytosis : Implications for Disease Pathology and Targeted Therapies - 26/09/23

Doi : 10.1016/j.iac.2023.04.008

Yannick Chantran, PharmD, PhD ^a,^b,^c, Peter Valent, MD ^d,^e, Michel Arock, PharmD, PhD ^a,^f,^⁎
^a Department of Biological Hematology, Pitié-Salpêtrière Hospital, DMU BioGem, AP-HP.Sorbonne University, Paris, France
^b Department of Biological Immunology, Saint-Antoine Hospital, DMU BioGem, AP-HP.Sorbonne University, Paris, France
^c Health Environmental Risk Assessment (HERA) Team, Centre of Research in Epidemiology and Statistics (CRESS), Inserm / INRAE, Faculty of Pharmacy, Université de Paris, Paris, France
^d Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Austria
^e Division of Hematology and Hemostaseology, Department of Internal Medicine, Medical University of Vienna
^f Department of Biological Hematology, Pitié-Salpêtrière Hospital, DMU BioGem, AP-HP.Sorbonne University, Paris, France

^∗Corresponding author. Department of Biological Hematology, DMU BioGem, Pitié-Salpêtrière Charles-Foix Hospital, AP-HP.Sorbonne University, 47/83 Bd de l’Hôpital, Paris 75013.Department of Biological HematologyDMU BioGemPitié-Salpêtrière Charles-Foix HospitalAP-HP.Sorbonne University47/83 Bd de l’HôpitalParis75013

Résumé

A KIT activating mutation (usually KIT D816V) is detected in neoplastic cells in greater than 90% of indolent patients with systemic mastocytosis (SM). In more advanced variants of SM, additional genetic defects can be found in several myeloid malignancy-related genes, which can be detected by applying next-generation sequencing. Currently, the techniques recommended to detect the KIT D816V mutation and quantify the mutational burden in peripheral blood, bone marrow, or other organs/tissues are allele specific-quantitative PCR or droplet digital PCR. These techniques are useful for diagnosis, prognostication, follow-up and monitoring of therapeutic efficacy of cytoreductive agents in patients with SM.

Le texte complet de cet article est disponible en PDF.

Keywords : Mast cells, Mastocytosis, KIT D816V mutation, Mutation burden, ASO-qPCR, ddPCR, Tyrosine kinase inhibitors

Plan

Key points

Introduction

Diagnostic criteria and classification of mastocytosis

The role of KIT mutations in the pathophysiology of mastocytosis

KIT D816V and Other KIT Mutations in Mastocytosis

Impact of the KIT D816V Mutant Receptor on Cell Survival and Proliferation

The role of non-KIT mutations in the pathophysiology and prognosis of different systemic mastocytosis variants

Methods to detect (and quantify) KIT mutations in mastocytosis

Quantification of the KIT D816V mutational burden for prognostication and monitoring of therapeutic efficacy

Quantification of the KIT D816V Mutational Burden for Prognostication of Systemic Mastocytosis

Monitoring of the Therapeutic Efficacy of Midostaurin and Avapritinib in Advanced Systemic Mastocytosis

Concluding remarks and open questions

Clinics care points

Disclosure

Export

Vol 43 - N° 4

P. 651-664 - novembre 2023 Retour au numéro

Article précédent

World Health Organization Classification and Diagnosis of Mastocytosis : Update 2023 and Future Perspectives
Peter Valent, Karl Sotlar, Hans-Peter Horny, Michel Arock, Cem Akin

| Article suivant

Pediatric and Hereditary Mastocytosis
Joanna Renke, Ninela Irga-Jaworska, Magdalena Lange

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

connectez-vous ou créez un compte

KIT Mutations and Other Genetic Defects in Mastocytosis : Implications for Disease Pathology and Targeted Therapies - 26/09/23

Résumé

Plan

Export citations

Fichier

Contenu

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL