High IDH1 Expression Is Associated with a Poor Prognosis in Cytogenetically Normal Acute Myeloid Leukemia

Ma, Qiuling; Wang, Jinghan; Wang, Yungui; Hu, Chao; Mu, Qitian; Yu, Mengxia; Wang, Lei; Wang, Dongmei; Yang, Min; Yin, Xiufeng; Chen, Feifei; Lu, Shasha; Chen, Jian; Zhu, Zhijuan; Chen, Sai‐Juan; Jin, Jie

doi:10.1182/blood.v124.21.5314.5314

Cited by 12 publications

(20 citation statements)

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“…In the normal karyotype group, frequency of IDH mutations was even higher with 47.6% of the patients being positive. Other authors reported higher frequency of IDH mutations in the group of AML patients with normal karyotype than when cytogenetic analysis was not taken into consideration (Marcucci et al reported 33%, [24] Emadi et al reported 25%, [25] Ma et al reported 21.56%) [26] but still the frequencies reported in their studies were less than that detected in our study.…”

Section: Discussioncontrasting

confidence: 77%

Study of Isocitrate Dehydrogenase 1and 2 Mutations in Adult Egyptian Patients with Denovo Acute Myeloblastic Leukemia, Their Relation to Clinical Characteristics, FLT3/ITD and Nucleophosmin 1 Mutations and Impact on Treatment Outcome

Barakat

Elsorady

Ayad

et al. 2019

IBRR

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Background: Acute myeloid leukaemia (AML) is a malignancy that is heterogeneous in nature characterized by genetic abnormalities some of which are established in the diagnosis and prognosis of the disease. An additional role for alterations in epigenetic mechanisms has been also highlighted in the pathogenesis of the disease. This may have a role in determining the disease outcome, impact the treatment decision and provide options for targeted therapies especially in patients who lack genetic aberrations. One of the modes of epigenetic dysregulation is mutation in genes encoding isocitrate dehydrogenase 1 and 2 that has been observed in AML with a higher incidence in patients with normal karyotype (NK). Aim of the work: The aim of this work was to study the frequency of IDH1 (R132) and IDH2 (R140Q, R172K) mutations in adult Egyptian patients with de novo acute myeloblastic leukemia (AML), their relation with clinical characteristics, other molecular markers (the internal tandem duplication (ITD)) mutation of FLT3 gene and NPM1 gene mutation) and impact on treatment outcome. Methods: Peripheral blood samples from 50 adult patients with denovo acute myeloid leukemia, admitted to the haematology unit at Alexandria Main University Hospital from February 2015 to February 2017, were used. The polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was used for detection of IDH1 codon R132 and IDH2 codons (R140, R172) mutations on genomic DNA. PCR was used for detection of FLT3-ITD mutation on genomic DNA. PCR was used for detection of NPM1 mutation on RNA. Results: IDH 1and 2 mutations occurred in 30% of newly diagnosed AML patients and 47.6% of NK patients. Both mutations did not co-occur except in one case. IDH positive patients were significantly older than IDH negative patients (p=0.003). There was no statistically significant correlation between any of the clinical parameters and the IDH mutations. FAB-M2 was the most common FAB subtype among IDH positive patients. No correlation between IDH mutations and NPM1 or FLT3 could be demonstrated. IDH positive patients had significantly lower CR rates after induction chemotherapy than IDH negative patients (p=0.021). Conclusion: IDH1, 2 mutations are recurring genetic alterations in AML with a higher incidence in patients with normal karyotype and they may have an unfavorable impact on clinical outcome in adult AML patients.

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Section: Discussioncontrasting

confidence: 77%

Study of Isocitrate Dehydrogenase 1and 2 Mutations in Adult Egyptian Patients with Denovo Acute Myeloblastic Leukemia, Their Relation to Clinical Characteristics, FLT3/ITD and Nucleophosmin 1 Mutations and Impact on Treatment Outcome

Barakat

Elsorady

Ayad

et al. 2019

IBRR

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“…DNA and RNA samples obtained from mononuclear cells from BM samples at primary diagnosis were extracted as described previously [ 9 ]. Mutation analyses of NPM1, FLT3-ITD, CEBPA, DNMT3A, IDH1 and IDH2 were carried out as described previously [ 9 ].…”

Section: Methodsmentioning

confidence: 99%

“…For example, low expression of the brain and acute leukemia cytoplasmic (BAALC) and ETS-related gene (ERG) genes have been associated with better outcome in CN-AML patients [ 7 , 8 ]. Recently, we found that high expression of HIP1 and IDH1 were associated with poor survival in AML [ 9 ]. In addition to genetic alterations in protein coding genes, aberrant expression of noncoding RNAs might play an important role in leukemia initiation and outcome prediction [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

MiR-362-5p as a novel prognostic predictor of cytogenetically normal acute myeloid leukemia

Wang

Yang

et al. 2018

J Transl Med

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BackgroundMicroRNAs are of special interest in cancer research and hold significant promise as diagnostic and prognostic biomarkers for malignant disease. MiR-362-5p have been found to exert both oncogenic and tumor suppressive effects depending highly on the cellular context. The aim of this study was to determine whether the expression of miR-362-5p can be served as a prognostic factor for patients with cytogentically normal acute myeloid leukemia (CN-AML).MethodsWe enrolled 224 patients with CN-AML and measured the expression of miR-362-5p by quantitative real time PCR analysis. We classified patients into high and low expression based on the median value. The Cox regression analyses were carried out to assess the prognostic significance of miR-362-5p expression in the context of the well-established predictors. Additionally, microRNA expression profiling were conducted to identify the biological insights between high and low group.ResultsHigh expressers had older age. High expressers obtained shorter overall survival in the univariate analysis. The independent prognostic value of miR-362-5p remained in the context of the well-established clinical and cytogenetic predictors. Moreover, the prognostic value of miR-362-5p was also validated in an independent cohort of CN-AML. Notably, numerous oncomiRs were also high expressed in high miR-362-5p group.ConclusionHigh miR-362-5p expression was associated with poorer overall survival implicating the oncogenic function in AML development.

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“…10 Mutation analyses of NPM1, FLT3-ITD, CEBPA, DNMT3A, IDH1 and IDH2 were carried out as described previously. 10…”

Section: Cytogenetic and Gene Mutation Analysismentioning

confidence: 99%

Prognostic utility of six mutated genes for older patients with acute myeloid leukemia

Wang

et al. 2017

Intl Journal of Cancer

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Approximately 50% of older patients with acute myeloid leukemia (AML) do not obtain chromosomal abnormalities as an effective risk-stratification, and present cytogenetically normal AML (CN-AML). To develop a reliable prediction model for stratifying the risk of these elderly patients, we conducted a study with a discovery and validation design. As a result, we found the top 6 mutated genes in the discovery cohort of 26 case by the whole exome sequencing, and verified as recurrent mutations in the large cohort of 329 patients by Sanger sequencing. The top 6 genes were NPM1, FLT3-ITD, DNMT3A, CEBPA double allele, IDH1 and IDH2 mutations, and the frequency of each gene in the combining cohort was 36.8%, 19.8%, 20.1%, 5.8%, 14.9% and 22.5%, respectively. In addition, clinical variables such as age, white blood cell counts, genes of IDH1 and DNMT3A mutations, European LeukemiaNet genotype (NPM1 mutations and lacking FLT3-ITD or CEBPA double allele mutations) and treatment protocols were independent factors for predicting the probabilities of overall and event-free survival. The prediction nomograms based on these significant factors showed accurate discrimination. In conclusion, we developed a reliable prediction model for stratifying the risk of elderly patients with CN-AML.

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High IDH1 Expression Is Associated with a Poor Prognosis in Cytogenetically Normal Acute Myeloid Leukemia

Cited by 12 publications

References 0 publications

Study of Isocitrate Dehydrogenase 1and 2 Mutations in Adult Egyptian Patients with Denovo Acute Myeloblastic Leukemia, Their Relation to Clinical Characteristics, FLT3/ITD and Nucleophosmin 1 Mutations and Impact on Treatment Outcome

Study of Isocitrate Dehydrogenase 1and 2 Mutations in Adult Egyptian Patients with Denovo Acute Myeloblastic Leukemia, Their Relation to Clinical Characteristics, FLT3/ITD and Nucleophosmin 1 Mutations and Impact on Treatment Outcome

MiR-362-5p as a novel prognostic predictor of cytogenetically normal acute myeloid leukemia

Prognostic utility of six mutated genes for older patients with acute myeloid leukemia

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