Details

Autor(en) / Beteiligte

• Stasik, Sebastian
• Eckardt, Jan-Niklas
• Kramer, Michael
• Röllig, Christoph
• Krämer, Alwin
• Scholl, Sebastian
• Hochhaus, Andreas
• Crysandt, Martina
• Brümmendorf, Tim H.
• Naumann, Ralph
• Steffen, Björn
• Kunzmann, Volker
• Einsele, Hermann
• Schaich, Markus
• Burchert, Andreas
• Neubauer, Andreas
• Schäfer-Eckart, Kerstin
• Schliemann, Christoph
• Krause, Stefan
• Herbst, Regina
• Hänel, Mathias
• Frickhofen, Norbert
• Noppeney, Richard
• Kaiser, Ulrich
• Baldus, Claudia D.
• Kaufmann, Martin
• Rácil, Zdenek
• Platzbecker, Uwe
• Berdel, Wolfgang E.
• Mayer, Jiri
• Serve, Hubert
• Müller-Tidow, Carsten
• Ehninger, Gerhard
• Bornhäuser, Martin
• Schetelig, Johannes
• Middeke, Jan M.
• Thiede, Christian

Titel

Impact of PTPN11 mutations on clinical outcome analyzed in 1529 patients with acute myeloid leukemia

Ist Teil von

• Blood advances, 2021-09, Vol.5 (17), p.3279-3289

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• The tyrosine-protein phosphatase nonreceptor type 11 (PTPN11) is an important regulator of RAS signaling and frequently affected by mutations in patients with acute myeloid leukemia (AML). Despite the relevance for leukemogenesis and as a potential therapeutic target, the prognostic role is controversial. To investigate the prognostic impact of PTPN11 mutations, we analyzed 1529 adult AML patients using next-generation sequencing. PTPN11 mutations were detected in 106 of 1529 (6.93%) patients (median VAF: 24%) in dominant (36%) and subclonal (64%) configuration. Patients with PTPN11 mutations were associated with concomitant mutations in NPM1 (63%), DNMT3A (37%), and NRAS (21%) and had a higher rate of European LeukemiaNet (ELN) favorable cytogenetics (57.8% vs 39.1%; P < .001) and higher white blood cell counts (P = .007) compared with PTPN11 wild-type patients. In a multivariable analysis, PTPN11 mutations were independently associated with poor overall survival (hazard ratio [HR]: 1.75; P < .001), relapse-free survival (HR: 1.52; P = .013), and a lower rate of complete remission (odds ratio: 0.46; P = .008). Importantly, the deleterious effect of PTPN11 mutations was confined predominantly to the ELN favorable-risk group and patients with subclonal PTPN11 mutations (HR: 2.28; P < .001) but not found with dominant PTPN11 mutations (HR: 1.07; P = .775), presumably because of significant differences within the rate and spectrum of associated comutations. In conclusion, our data suggest an overall poor prognostic impact of PTPN11 mutations in AML, which is significantly modified by the underlying cytogenetics and the clonal context in which they occur. •PTPN11 mutations are recurrent alterations in patients with AML and are an independent prognostic factor for poor survival.•The deleterious effect is confined mostly to patients within the ELN favorable risk group and subclonal constellations of PTPN11 mutations. [Display omitted]