Clinical characteristics and prognostic analysis of acute myeloid leukemia patients with PTPN11 mutations

Sun, Yueyue; Zhang, Fenghong; Huo, Li; Cai, Wenzhi; Wang, Qinrong; Wen, Lijun; Yan, Litao; Shen, Hongjie; Xu, Xiaoyu; Chen, Suning

doi:10.1080/16078454.2022.2140274

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…Some studies showed that PTPN11 mut were associated with shorter OS. 10 , 11 , 17 , 19 However, others reported that the median OS was similar in both the PTPN11 mut and PTPN11 wt groups. 15 , 20 Metzeler et al.…”

Section: Discussionmentioning

confidence: 96%

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The clinical features and prognostic implications of PTPN11 mutation in adult patients with acute myeloid leukemia in China

Yang,

Zhao,

et al. 2023

Cancer Medicine

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BackgroundThe clinical significance of protein tyrosine phosphatase nonreceptor type 11 mutation (PTPN11mut) in acute myeloid leukemia (AML) is underestimated.MethodsWe collected the data of AML patients with mutated PTPN11 and wild‐type PTPN11 (PTPN11wt) treated at our hospital and analyzed their clinical characteristics and prognosis.ResultsFifty‐nine PTPN11mut and 124 PTPN11wt AML patients were included. PTPN11mut was more common in myelomonocytic and monocytic leukemia, and was more likely to co‐mutate with KRAS, KMT2C, NRAS, U2AF1, NOTCH1, IKZF1, and USH2A mutations than PTPN11wt. The overall survival for AML patients with PTPN11mut was significantly shorter than that for those with PTPN11wt (p = 0.03). The negative impact of PTPN11mut on overall survival was pronounced in the “favorable” and “intermediate” groups of ELN2017 risk stratification, as well as in the wild‐type NPM1 group (p = 0.01, p = 0.01, and p = 0.04).ConclusionPTPN11mut is associated with distinct clinical and molecular characteristics, and adverse prognosis in AML patients.

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Section: Discussionmentioning

confidence: 96%

“…The impacts of PTPN11 mut on OS in AML patients are controversial. Some studies showed that PTPN11 mut were associated with shorter OS 10,11,17,19 . However, others reported that the median OS was similar in both the PTPN11 mut and PTPN11 wt groups 15,20 .…”

Section: Discussionmentioning

confidence: 99%

The clinical features and prognostic implications of PTPN11 mutation in adult patients with acute myeloid leukemia in China

Yang,

Zhao,

et al. 2023

Cancer Medicine

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“… 29 PTPN11 mutations may co-occur more commonly with DNMT3A , NPM1 , and FLT3-ITD mutations. 30 Furthermore, PTPN11 mutations exhibit a discernible link with diminished response to treatment interventions and a less favorable disease outcome in AML, with several reports fully defining the clinical characteristics and prognostic impact of PTPN11 -mutated AML. 31 , 32 , 33 Studies on PTPN11 -mutated juvenile myelomonocytic leukemia have shown that a combination of 5-Aza, trametinib, and chemotherapy might result in a better clinical response.…”

Section: Discussionmentioning

confidence: 99%

Next-generation sequencing reveals relapse and leukemia-free survival risks in newly diagnosed acute myeloid leukemia treated with CAG regimen combined with decitabine

Huang,

Chen,

Wang

et al. 2024

Cancer Pathogenesis and Therapy

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“…Genomic DNA was extracted from bone marrow samples following the manufacturer's protocols (QIAGEN). A targeted NGS panel covering 172 frequently mutated genes in haematological malignancies was applied to detect gene mutations as previous 13 . Analytical sensitivity was established at 1% mutant reads on a background of total reads.…”

Section: Methodsmentioning

confidence: 99%

Mutation spectrum of FLT3 and significance of non‐canonical FLT3 mutations in haematological malignancy

Qiu

Dai

et al. 2023

Br J Haematol

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Summary Fms‐like tyrosine kinase 3 (FLT3) is frequently mutated in haematological malignancies. Although canonical FLT3 mutations including internal tandem duplications (ITDs) and tyrosine kinase domains (TKDs) have been extensively studied, little is known about the clinical significance of non‐canonical FLT3 mutations. Here, we first profiled the spectrum of FLT3 mutations in 869 consecutively newly diagnosed acute myeloid leukaemia (AML), myelodysplastic syndrome and acute lymphoblastic leukaemia patients. Our results showed four types of non‐canonical FLT3 mutations depending on the affected protein structure: namely non‐canonical point mutations (NCPMs) (19.2%), deletion (0.7%), frameshift (0.8%) and ITD outside the juxtamembrane domain (JMD) and TKD1 regions (0.5%). Furthermore, we found that the survival of patients with high‐frequency (>1%) FLT3‐NCPM in AML was comparable to those with canonical TKD. In vitro studies using seven representative FLT3‐deletion or frameshift mutant constructs showed that the deletion mutants of TKD1 and the FLT3‐ITD mutant of TKD2 had significantly higher kinase activity than wild‐type FLT3, whereas the deletion mutants of JMD had phosphorylation levels comparable with wild‐type FLT3. All tested deletion mutations and ITD were sensitive to AC220 and sorafenib. Collectively, these data enrich our understanding of FLT3 non‐canonical mutations in haematological malignancies. Our results may also facilitate prognostic stratification and targeted therapy of AML with FLT3 non‐canonical mutations.

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Clinical characteristics and prognostic analysis of acute myeloid leukemia patients with PTPN11 mutations

Cited by 7 publications

References 29 publications

The clinical features and prognostic implications of PTPN11 mutation in adult patients with acute myeloid leukemia in China

The clinical features and prognostic implications of PTPN11 mutation in adult patients with acute myeloid leukemia in China

Next-generation sequencing reveals relapse and leukemia-free survival risks in newly diagnosed acute myeloid leukemia treated with CAG regimen combined with decitabine

Mutation spectrum of FLT3 and significance of non‐canonical FLT3 mutations in haematological malignancy

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