Molecular profiling of myeloid progenitor cells in multi-mutated advanced systemic mastocytosis identifies KIT D816V as a distinct and late event

• Verfasst von: Jawhar, Mohamad [VerfasserIn]
• Verfasst von: Schwaab, Juliana [VerfasserIn]
• Verfasst von: Metzgeroth, Georgia [VerfasserIn]
• Verfasst von: Müller, Nadine Zoé [VerfasserIn]
• Verfasst von: Schneider, Sven [VerfasserIn]
• Verfasst von: Naumann, Nicole [VerfasserIn]
• Verfasst von: Hofmann, Wolf-Karsten [VerfasserIn]
• Verfasst von: Fabarius, Alice [VerfasserIn]
• Verfasst von: Reiter, Andreas [VerfasserIn]
• Titel: Molecular profiling of myeloid progenitor cells in multi-mutated advanced systemic mastocytosis identifies KIT D816V as a distinct and late event
• Verf.angabe: M. Jawhar, J. Schwaab, S. Schnittger, K. Sotlar, H.-P. Horny, G. Metzgeroth, N. Müller, S. Schneider, N. Naumann, C. Walz, T. Haferlach, P. Valent, W.-K. Hofmann, N.C.P. Cross, A. Fabarius and A. Reiter
• Umfang: 8 S.
• Fussnoten: Gesehen am 01.02.2018
• Titel Quelle: Enthalten in: Leukemia
• Jahr Quelle: 2015
• Band/Heft Quelle: 29(2015), 5, S. 1115-1122
• ISSN Quelle: 1476-5551
• DOI: doi:10.1038/leu.2015.4
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1568022220

Abstract

To explore the molecular profile and its prognostic implication in systemic mastocytosis (SM), we analyzed the mutation status of granulocyte–macrophage colony-forming progenitor cells (CFU-GM) in patients with KIT D816V+ indolent SM (ISM, n=4), smoldering SM (SSM, n=2), aggressive SM (ASM, n=1), SM with associated clonal hematologic non-mast cell lineage disorder (SM-AHNMD, n=5) and ASM-AHNMD (n=7). All patients with (A)SM-AHNMD (n=12) carried 1–4 (median 3) additional mutations in 11 genes tested, most frequently TET2, SRSF2, ASXL1, CBL and EZH2. In multi-mutated (A)SM-AHNMD, KIT D816V+ single-cell-derived CFU-GM colonies were identified in 8/12 patients (median 60%, range 0–95). Additional mutations were identified in CFU-GM colonies in all patients, and logical hierarchy analysis indicated that mutations in TET2, SRSF2 and ASXL1 preceded KIT D816V. In ISM/SSM, no additional mutations were detected and CFU-GM colonies were exclusively KIT D816V−. These data indicate that (a) (A)SM-AHNMD is a multi-mutated neoplasm, (b) mutations in TET2, SRSF2 or ASXL1 precede KIT D816V in ASM-AHNMD, (c) KIT D816V is thus a phenotype modifier toward SM and (d) KIT D816V or other mutations are rare in CFU-GM colonies of ISM/SSM patients, which might explain at least in part their better prognosis.