IDH1 and IDH2 mutations in patients with acute myeloid leukemia: Suitable targets for minimal residual disease monitoring?

Petrova, Lucie; Vrbacky, Filip; Lánska, M.; Zavřelová, Alžběta; Зак, Павел; Hrochová, Kateřina

doi:10.1016/j.clinbiochem.2018.08.012

Cited by 29 publications

(37 citation statements)

References 20 publications

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“…However, not all those covered extra regions have been reported as clinically relevant, and sequencing them lessens the read depth of the regions useful for clinical purposes. For example, out of the 12 exons of IDH1 gene, only mutations in exon 4 have been reported as deleterious [71] [72].…”

Section: Common Sequencing Errors Detected In the Ngs Panelsmentioning

confidence: 99%

Assessment of the clinical utility of four NGS panels in myeloid malignancies. Suggestions for NGS panel choice or design

et al. 2020

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The diagnosis of myeloid neoplasms (MN) has significantly evolved through the last few decades. Next Generation Sequencing (NGS) is gradually becoming an essential tool to help clinicians with disease management. To this end, most specialized genetic laboratories have implemented NGS panels targeting a number of different genes relevant to MN. The aim of the present study is to evaluate the performance of four different targeted NGS gene panels based on their technical features and clinical utility. A total of 32 patient bone marrow samples were accrued and sequenced with 3 commercially available panels and 1 custom panel. Variants were classified by two geneticists based on their clinical relevance in MN. There was a difference in panel's depth of coverage. We found 11 discordant clinically relevant variants between panels, with a trend to miss long insertions. Our data show that there is a high risk of finding different mutations depending on the panel of choice, due both to the panel design and the data analysis method. Of note, CEBPA, CALR and FLT3 genes, remains challenging the use of NGS for diagnosis of MN in compliance with current guidelines. Therefore, conventional molecular testing might need to be kept in place for the correct diagnosis of MN for now. OPEN ACCESS Citation: Aguilera-Diaz A, Vazquez I, Ariceta B, Mañú A, Blasco-Iturri Z, Palomino-Echeverría S, et al. (2020) Assessment of the clinical utility of four NGS panels in myeloid malignancies. Suggestions for NGS panel choice or design. PLoS ONE 15(1): e0227986. https://doi.org/10.

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Section: Common Sequencing Errors Detected In the Ngs Panelsmentioning

confidence: 99%

Assessment of the clinical utility of four NGS panels in myeloid malignancies. Suggestions for NGS panel choice or design

et al. 2020

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“…The prognostic significance of IDH2 mutation at diagnosis is not completely clear and even less clear is the persistence of IDH2 mutation after chemotherapy, therefore the role of IDH2 mutation as a marker of MRD needs investigation [12]. In clinical practice, the evaluation of IDH2 mutations allows a targeted therapeutic choice, based on a specific IDH2 selective inhibitor (Enasidenib) [28,29]. Frequently the mutated clones at diagnosis are small with a variant allele frequency (VAF) less than 20%, the limit of detection of Sanger sequencing.…”

Section: Discussionmentioning

confidence: 99%

Highly Sensitive Detection of IDH2 Mutations in Acute Myeloid Leukemia

Petiti

Rosso

Croce

et al. 2020

JCM

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Background: Acute myeloid leukemia is a heterogeneous hematological disease, characterized by karyotypic and molecular alterations. Mutations in IDH2 have a role in diagnosis and as a minimal residue disease marker. Often the variant allele frequency during follow up is less than 20%, which represents the limit of detection of Sanger sequencing. Therefore, the development of sensitive methodologies to identify IDH2 mutations might help to monitor patients’ response to therapy. We compared three different methods to identify and monitor IDH2 mutations in patients’ specimens. Methods: Performances of PNA-PCR clamping, droplet digital PCR and Sanger for IDH2 status identification were evaluated and compared in 96 DNA patients’ specimens. Results: In contrast with Sanger sequencing, our results highlighted the concordance between PNA clamping and digital PCR. Furthermore, PNA-PCR clamping was able to detect more mutated DNA with respect to Sanger sequencing that showed several false negatives independently from the allelic frequency. Conclusions: We found that PNA-PCR clamping and digital PCR identified IDH2 mutations in DNA samples with comparable results in a percentage significantly higher compared to Sanger sequencing. PNA-PCR clamping can be used even in laboratories not equipped for sophisticated analyses, decreasing cost and time for IDH2 characterization.

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“…32,33 There are studies reporting the stability and suitability of IDH as a marker of MRD. 32,34 Recently, Petrova t al 35 published the evaluation of MRD in 90 patients, 22% of them with IDH1/IDH2 mutations. They based the assessment on NGS and ddPCR.…”

Section: Idh1/idh2mentioning

confidence: 99%

“…Few studies have been published on MRD by ddPCR. We have already mentioned the study by Petrova et al 35 based on IDH1/2 mutation. This technique has also been explored by Brambati et al 34 in the setting of allogeneic bone marrow transplantation to identify the reappearance of small mutated clones of the recipient.…”

Section: Digital Pcrmentioning

confidence: 99%

<p>Strategies for minimal residual disease detection: current perspectives</p>

Andreani¹,

Cilloni²

2019

BLCTT

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Currently, the post-remission treatment in acute leukemia is based on the genetic profile of leukemic cells at diagnosis (ie, FLT3 ITD positivity) and on the level of measurable residual disease (MRD) after induction and consolidation chemotherapy. Two methods are currently preferred for MRD evaluation in many centers: multiparameter flow cytometry and real-time quantitative PCR. Additional methods such as next-generation sequencing and digital PCR are under investigation, in an attempt to increase the sensitivity and thus allowing the detection of small clones. Many studies suggest that MRD positivity after chemotherapy is associated with negative prognosis, and the reappearance of MRD during follow-up allows impending relapse to be identified and consequently enables early intervention. Finally, MRD positivity before hematopoietic stem cell transplantation is predictive of the outcome. Although the significance of MRD in acute leukemia has been widely explored, the assessment of molecular MRD is not yet a routine practice. In this review, we describe the significance of MRD in different settings and the main markers and methods used for MRD detection.

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IDH1 and IDH2 mutations in patients with acute myeloid leukemia: Suitable targets for minimal residual disease monitoring?

Cited by 29 publications

References 20 publications

Assessment of the clinical utility of four NGS panels in myeloid malignancies. Suggestions for NGS panel choice or design

Assessment of the clinical utility of four NGS panels in myeloid malignancies. Suggestions for NGS panel choice or design

Highly Sensitive Detection of IDH2 Mutations in Acute Myeloid Leukemia

<p>Strategies for minimal residual disease detection: current perspectives</p>

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