WT1 mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its incorporation into a survival scoring system

Hou, Hsin‐An; Huang, Tai‐Chung; Lin, Liang-In; Liu, Chieh‐Yu; Chen, Chien-Yuan; Chou, Wen‐Chien; Tang, Jih-Luh; Tseng, Mei‐Hsuan; Huang, Chih‐Fen; Chiang, Yu‐Chih; Lee, Fen‐Yu; Liu, Ming-Chih; Yao, Ming; Huang, Shang-Yi; Ko, Bor-Sheng; Hsu, Szu-Chun; Wu, Shang‐Ju; Tsay, Woei; Chen, Yao‐Chang; Tien, Hwei‐Fang

doi:10.1182/blood-2009-12-259390

Cited by 155 publications

(113 citation statements)

References 37 publications

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“…The mutations were confirmed by at least two repeated analyses. Detection of mutations in other genes, including IDH1 [27], IDH2 [28], JAK2 [29], MLL/PTD [30], RUNX1 [31], FLT3/ ITD [32], WT1 [33], N-RAS, K-RAS [34], ASXL1 [35], DNMT3 [36], and EZH2 [37] was performed as described previously. Sequential studies during clinical courses were performed in 421 samples from 142 patients.…”

Section: Mutation Analysesmentioning

confidence: 99%

Clinical implications of U2AF1 mutation in patients with myelodysplastic syndrome and its stability during disease progression

Tang

Lin

et al. 2013

American J Hematol

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We aimed to analyze clinical impacts of the U2AF1 mutation on patients with myelodysplastic syndrome (MDS) and its stability during disease progression. We checked mutation status of the U2AF1 by direct sequencing in 478 de novo MDS patients and correlated with the clinical characteristics and outcomes. We also sequentially analyzed the U2AF1 mutation in 421 samples from 142 patients to determine its stability during the disease courses. Thirty-six patients (7.5%) were found to have U2AF1 mutations, which occurred more frequently in younger patients (P 5 0.033). U2AF1 mutation was an independent poor-risk factor for overall survival (OS) in all patients (P 5 0.030) and younger patients (P 5 0.041). U2AF1 mutation could also predict shorter time-to-leukemia transformation (TTL) in younger patients (P 5 0.020). In addition, U2AF1 mutation was associated with shorter TTL in lower-risk MDS patients. Sequential analyses showed all original U2AF1 mutations in U2AF1-mutated patients were retained during follow-ups unless complete remission was achieved, whereas none of the U2AF1-wild patients acquired a novel mutation during disease evolution. U2AF1 mutation is more prevalent in younger MDS patients and associated with inferior outcomes although it is stable during the clinical course. The mutation may be used as a biomarker for risk stratification. Am. J. Hematol. 88:E277-E282,

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Section: Mutation Analysesmentioning

confidence: 99%

Clinical implications of U2AF1 mutation in patients with myelodysplastic syndrome and its stability during disease progression

Tang

Lin

et al. 2013

American J Hematol

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“…Mutation analyses were performed on CEBPA in the only exon, 20 WT1 in exons 7, 8 and 9, 21 MLL-PTD that spanned exons 2-8, 22 JAK2 on V617F hot spot, 23 PTPN11 in exons 3 and 13, 24 RUNX1 in exons 3-8, 25 c-KIT in exons 8, 10, 11, 12 and 17, 26 RAS on codons 12 and 13, and 61 in exons 1 and 2, 27 FLT3-TKD on codon D835, 28 IDH1 on R132 hotspot, 14 ASXL1 in exon 12, 29 NPM1 on hotspot involving the C terminal portion of the transcript with a four nucleotides insertion between positions 960 and 961, 30 and FLT3-ITD in exon 14 31 as described previously. Mutations were detected by direct sequencing on the PCR products, and the sensitivity of each assay was about 15%.…”

Section: Mutation Analysismentioning

confidence: 99%

The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia

et al. 2010

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Although the clinical features of the Isocitrate dehydrogenase 2 (IDH2) mutation in acute myeloid leukemia (AML) have been characterized, its prognostic significance remains controversial and its stability has not been investigated. We analyzed 446 adults with primary non-M3 AML and found IDH2 R172, R140 and IDH1 R132 mutations occurred at a frequency of 2.9, 9.2 and 6.1%, respectively. Compared with wild-type IDH2, mutation of IDH2 was associated with higher platelet counts, intermediate-risk or normal karyotype and isolated þ 8, but was inversely correlated with expression of HLA-DR, CD34, CD15, CD7 and CD56, and was mutually exclusive with WT1 mutation and chromosomal translocations involving core-binding factors. All these correlations became stronger when IDH1 and IDH2 mutations were considered together. Multivariate analysis revealed IDH2 mutation as an independent favorable prognostic factor. IDH2 À /FLT3-ITD þ genotype conferred especially negative impact on survival. Compared with IDH2 R140 mutation, IDH2 R172 mutation was associated with younger age, lower white blood cell count and lactate dehydrogenase level, and was mutually exclusive with NPM1 mutation. Serial analyses of IDH2 mutations at both diagnosis and relapse in 121 patients confirmed high stability of IDH2 mutations. In conclusion, IDH2 mutation is a stable marker during disease evolution and confers favorable prognosis.

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“…Gaidzik et al concluded that WT1 mutation as a single molecular marker did not have an impact on outcome. On the other hand, Hou et al demostrated that WT1 mutations disappeared in WT1-mutated studied patients who achieved complete remission, suggesting its potential use as MRD marker (Gaidzik et al, 2009;Hou et al, 2010). Fig.…”

Section: Wt1mentioning

confidence: 99%

New Molecular Markers in Acute Myeloid Leukemia

Iglesia¹,

Casares²,

Jorge³

et al. 2011

Myeloid Leukemia - Basic Mechanisms of Leukemogenesis

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WT1 mutation in 470 adult patients with acute myeloid leukemia: stability during disease evolution and implication of its incorporation into a survival scoring system

Cited by 155 publications

References 37 publications

Clinical implications of U2AF1 mutation in patients with myelodysplastic syndrome and its stability during disease progression

Clinical implications of U2AF1 mutation in patients with myelodysplastic syndrome and its stability during disease progression

The prognostic impact and stability of Isocitrate dehydrogenase 2 mutation in adult patients with acute myeloid leukemia

New Molecular Markers in Acute Myeloid Leukemia

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