Frequency and clinical impact of WT1 mutations in the context of CEBPA-mutated acute myeloid leukemia
Introduction Several studies have confirmed that mutations in the Wilms tumor 1 (WT1) gene occur in adult acute myeloid leukemia (AML). However, few data are available regarding the incidence of WT1 mutations in CEBPAmut AML and their impact.Methods We retrospectively analyzed the frequency and clinical impact of WT1 mutations in 220 newly diagnosed AML patients with CEBPA mutations(CEBPAmut). Chromosome karyotype analysis was performed by R or G banding method and further confirmed either by fluorescence in situ hybridization (FISH) and/or by multiple reverse transcription polymerase chain reaction (multiple RT–PCR). Mutations were detected with a panel of 112mutational genes using next-generation sequencing (NGS).Results Overall, 30 WT1 mutations were detected in 29 of the 220 CEBPAmut AML patients (13.18%) screened. These mutations clustered overwhelmingly in exon 7 (n=16). WT1 mutations were found to be significantly more frequent in AML patients with double-mutated CEBPA (CEBPAdm) than in AML patients with single-mutated CEBPA (17.36%vs. 8.08%, P = 0.043). Among WT1-mutated patients, the most common co-mutation was FLT3-ITD (n = 7, 24.14%), followed by NRAS (n = 5, 17.24%), CSF3R (n = 4, 13.79%), GATA2 (n = 4, 13.79%), and KIT (n = 4, 13.79%). The most frequent functional pathway was signaling pathways inas many as 62.07% of cases. Notably,the concomitant mutations in epigenetic regulatorswere inversely correlated with WT1 mutations(P = 0.003). CEBPAdm AML patients with WT1 mutations had inferior relapse-free survival, event-free survival and overall survival compared with patients CEBPAdm AML without WT1 mutations (P = 0.002, 0.004, and 0.010, respectively).Conclusion Our data showed that WT1 mutations are frequently identified in CEBPAmut AML, especially in CEBPAdm AML. CEBPAmut AML patients with WT1 mutations show distinct spectrum of comutations. In the context of CEBPAdm AML, WT1 mutations predict a poor prognosis..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
|---|---|
| Enthalten in: |
Hematology - 27(2022), 1, Seite 994-1002 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Ting Wang [VerfasserIn] |
|---|
| Links: |
doi.org [kostenfrei] |
|---|
| Themen: |
Acute myeloid leukemia |
|---|
| doi: |
10.1080/16078454.2022.2103964 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
DOAJ012197300 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ012197300 | ||
| 003 | DE-627 | ||
| 005 | 20230307030536.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230225s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/16078454.2022.2103964 |2 doi | |
| 035 | |a (DE-627)DOAJ012197300 | ||
| 035 | |a (DE-599)DOAJdc842811e7404d99974cd29b453ebbe8 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 050 | 0 | |a RC633-647.5 | |
| 100 | 0 | |a Ting Wang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Frequency and clinical impact of WT1 mutations in the context of CEBPA-mutated acute myeloid leukemia |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Introduction Several studies have confirmed that mutations in the Wilms tumor 1 (WT1) gene occur in adult acute myeloid leukemia (AML). However, few data are available regarding the incidence of WT1 mutations in CEBPAmut AML and their impact.Methods We retrospectively analyzed the frequency and clinical impact of WT1 mutations in 220 newly diagnosed AML patients with CEBPA mutations(CEBPAmut). Chromosome karyotype analysis was performed by R or G banding method and further confirmed either by fluorescence in situ hybridization (FISH) and/or by multiple reverse transcription polymerase chain reaction (multiple RT–PCR). Mutations were detected with a panel of 112mutational genes using next-generation sequencing (NGS).Results Overall, 30 WT1 mutations were detected in 29 of the 220 CEBPAmut AML patients (13.18%) screened. These mutations clustered overwhelmingly in exon 7 (n=16). WT1 mutations were found to be significantly more frequent in AML patients with double-mutated CEBPA (CEBPAdm) than in AML patients with single-mutated CEBPA (17.36%vs. 8.08%, P = 0.043). Among WT1-mutated patients, the most common co-mutation was FLT3-ITD (n = 7, 24.14%), followed by NRAS (n = 5, 17.24%), CSF3R (n = 4, 13.79%), GATA2 (n = 4, 13.79%), and KIT (n = 4, 13.79%). The most frequent functional pathway was signaling pathways inas many as 62.07% of cases. Notably,the concomitant mutations in epigenetic regulatorswere inversely correlated with WT1 mutations(P = 0.003). CEBPAdm AML patients with WT1 mutations had inferior relapse-free survival, event-free survival and overall survival compared with patients CEBPAdm AML without WT1 mutations (P = 0.002, 0.004, and 0.010, respectively).Conclusion Our data showed that WT1 mutations are frequently identified in CEBPAmut AML, especially in CEBPAdm AML. CEBPAmut AML patients with WT1 mutations show distinct spectrum of comutations. In the context of CEBPAdm AML, WT1 mutations predict a poor prognosis. | ||
| 650 | 4 | |a Acute myeloid leukemia | |
| 650 | 4 | |a WT1 | |
| 650 | 4 | |a CEBPA | |
| 650 | 4 | |a mutation | |
| 653 | 0 | |a Diseases of the blood and blood-forming organs | |
| 700 | 0 | |a Haiying Hua |e verfasserin |4 aut | |
| 700 | 0 | |a Zheng Wang |e verfasserin |4 aut | |
| 700 | 0 | |a Biao Wang |e verfasserin |4 aut | |
| 700 | 0 | |a Liujun Cao |e verfasserin |4 aut | |
| 700 | 0 | |a Wei Qin |e verfasserin |4 aut | |
| 700 | 0 | |a Pin Wu |e verfasserin |4 aut | |
| 700 | 0 | |a Xiaohui Cai |e verfasserin |4 aut | |
| 700 | 0 | |a Hongying Chao |e verfasserin |4 aut | |
| 700 | 0 | |a XuZhang Lu |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t Hematology |d Taylor & Francis Group, 2019 |g 27(2022), 1, Seite 994-1002 |w (DE-627)DOAJ000028797 |x 16078454 |7 nnns |
| 773 | 1 | 8 | |g volume:27 |g year:2022 |g number:1 |g pages:994-1002 |
| 856 | 4 | 0 | |u https://doi.org/10.1080/16078454.2022.2103964 |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/dc842811e7404d99974cd29b453ebbe8 |z kostenfrei |
| 856 | 4 | 0 | |u https://www.tandfonline.com/doi/10.1080/16078454.2022.2103964 |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/1607-8454 |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 951 | |a AR | ||
| 952 | |d 27 |j 2022 |e 1 |h 994-1002 | ||