High frequency of clonal hematopoiesis in Erdheim-Chester disease

Fleur Cohen Aubart, Damien Roos-Weil, Marine Armand, Alice Marceau-Renaut, Jean François Emile, Nicolas Duployez, Frédéric Charlotte, Sté Phanie Poulain, Raphael Lhote, Zofia Hé Lias-Rodzewicz, Véronique Della-Valle, Olivier Bernard, Karim Maloum, Florence Nguyen-Khac, Jean Donadieu, Zahir Amoura, Omar Abdel-Wahab, Julien Haroche

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    Résumé

    Erdheim-Chester disease (ECD) is a clonal hematopoietic disorder characterized by the accumulation of foamy histiocytes within organs (in particular, frequent retroperitoneal involvement) and a high frequency of BRAFV600E mutations. Although ECD is not commonly recognized to have overt peripheral blood (PB) or bone marrow (BM) disease, we recently identified that ECD patients have a high frequency of a concomitant myeloid malignancy. We thus conducted a systematic clinical and molecular analysis of the BM from 120 ECD patients. Surprisingly, 42.5% of ECD patients (51 of 120) had clonal hematopoiesis whereas 15.8% of patients (19 of 120) developed an overt hematologic malignancy (nearly all of which were a myeloid neoplasm). The most frequently mutated genes in BM were TET2, ASXL1, DNMT3A, and NRAS. ECD patients with clonal hematopoiesis were more likely to be older (P < .0001), have retroperitoneal involvement (P = .02), and harbor a BRAFV600E mutation (P = .049) than those without clonal hematopoiesis. The presence of the TET2 mutation was associated with a BRAFV600E mutation in tissue ECD lesions (P = .0006) and TET2-mutant ECD patients were more likely to have vascular involvement than TET2 wildtype ECD patients. Clonal hematopoiesis mutations in ECD were detected in cells derived from CD34+CD38- BM progenitors and PB monocytes but less frequently present in PB B and T lymphocytes. These data identify a heretofore unrecognized high frequency of clonal hematopoiesis in ECD patients, reaffirm the development of additional high risk of myeloid neoplasms in ECD, and provide evidence of a BM-based precursor cell of origin for many patients with ECD.

    langue originaleAnglais
    Pages (de - à)485-492
    Nombre de pages8
    journalBlood
    Volume137
    Numéro de publication4
    Les DOIs
    étatPublié - 28 janv. 2021

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