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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F21%3A00074698" target="_blank" >RIV/65269705:_____/21:00074698 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/21:00122748

Result on the web

<a href="https://ashpublications.org/bloodadvances/article/5/17/3279/476654/Impact-of-PTPN11-mutations-on-clinical-outcome" target="_blank" >https://ashpublications.org/bloodadvances/article/5/17/3279/476654/Impact-of-PTPN11-mutations-on-clinical-outcome</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1182/bloodadvances.2021004631" target="_blank" >10.1182/bloodadvances.2021004631</a>

Result language

angličtina

Original language name

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

Original language description

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 &lt; .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 &lt; .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 &lt; .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.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30205 - Hematology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Blood Advances

ISSN

2473-9529

e-ISSN

—

Volume of the periodical

5

Issue of the periodical within the volume

17

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

11

Pages from-to

3279-3289

UT code for WoS article

000702743800004

EID of the result in the Scopus database

2-s2.0-85114827674