Phenotypic and genotypic characteristics of mastocytosis according to the age of onset.

International audienceAdult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73%) in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001). 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001). Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001). In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy

Leucémie à tricholeucocytes (rôle de B-RAF dans la physiopathologie et innovations thérapeutiques)

PARIS-BIUP (751062107) / SudocSudocFranceF

Le rituximab dans le traitement du lymphome folliculaire

PARIS-BIUP (751062107) / SudocSudocFranceF

L'anémie liée à l'insuffisance rénale chronique et traitements

PARIS-BIUP (751062107) / SudocSudocFranceF

Physiopathologie du syndrome 5q- et intérêt thérapeutique du lénalidomide

PARIS-BIUP (751062107) / SudocSudocFranceF

La leucémie myéloïde chronique (intérêts et limites du traitement par l'imatinib (Glivec®))

PARIS-BIUP (751062107) / SudocSudocFranceF

Physiopathologie de la leucémie lymphoïde chronique

PARIS-BIUP (751062107) / SudocSudocFranceF

Le myélome multiple (physiopathologie et traitements)

PARIS-BIUP (751062107) / SudocSudocFranceF

Clinical and biological impact of ATP-binding cassette transporter activity in adult acute myeloid leukemia

International audienceChemotherapy resistance is the main cause of treatment failure in acute myeloid leukemia (AML) and has been related to ATP-binding cassette (ABC) transporter activity. However, the links between ABC activity, immunophenotype, and molecular AML parameters have been poorly evaluated. Moreover, the prognostic value of ABC activity, when compared to new molecular markers, is unknown. Here we investigated the links between ABC activity, as evaluated by JC-1 +/- cyclosporine A assay, and immunophenotypic, cytogenetic, molecular, and targeted next-generation sequencing features in 361 AML patients. High ABC activity was found in 164 patients and was significantly associated with less proliferating disease, an immature immunophenotype (expression of CD34, HLA-DR, CD117, CD13), and gene mutations defining AML as belonging to secondary-type ontogenic groups. Low ABC activity was associated with more mature myeloid differentiation (CD34-, cyMPO+, CD15+, CD33+) or monocytic commitment (CD64+, CD4+weak, CD14+), with NPM1 mutations, KMT2A rearrangements, and core-binding factor gene fusions, hallmarks of the de novo-type AML ontogeny. ABC activity was one of the major factors we identified using a random forest model for early prediction of AML ontogeny. In the 230 patients evaluated at diagnosis and intensively treated, high ABC activity was a predictive factor for primary resistance, and in multivariate analysis including full molecular data, an independent factor for event-free survival (P=0.0370). JC-1 +/- cyclosporine A assay could be used at diagnosis to predict AML ontogeny and to complete prognosis evaluation in addition to new molecular markers