Broad genomic workup including optical genome mapping uncovers a DDX3X: MLLT10 gene fusion in acute myeloid leukemia

Nilius‐Eliliwi, Verena; Tembrink, Marco; Gerding, Wanda M.; Lubieniecki, Krzystof P.; Lubieniecka, Joanna M.; Kankel, Stefanie; Liehr, Thomas; Mika, Thomas; Dimopoulos, Fotios; Döhner, Konstanze; Schroers, Roland; Nguyen, Hoa Huu Phuc; Vangala, Deepak B.

doi:10.3389/fonc.2022.959243

Cited by 5 publications

(10 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As an example, we detected a DDX3X::MLLT10 fusion in a female AML patient. So far, this variant has only been described in rare male cases and mostly in T-ALL patients [ 38 ]. MLLT10 is a common fusion partner of KMT2A .…”

Section: Ogm As a Tool For Detecting Novel Variantsmentioning

confidence: 99%

Optical Genome Mapping for Cytogenetic Diagnostics in AML

Nilius‐Eliliwi

Gerding

Schroers

et al. 2023

Cancers

Self Cite

View full text Add to dashboard Cite

The classification and risk stratification of acute myeloid leukemia (AML) is based on reliable genetic diagnostics. A broad and expanding variety of relevant aberrations are structural variants beyond single-nucleotide variants. Optical Genome Mapping is an unbiased, genome-wide, amplification-free method for the detection of structural variants. In this review, the current knowledge of Optical Genome Mapping (OGM) with regard to diagnostics in hematological malignancies in general, and AML in specific, is summarized. Furthermore, this review focuses on the ability of OGM to expand the use of cytogenetic diagnostics in AML and perhaps even replace older techniques such as chromosomal-banding analysis, fluorescence in situ hybridization, or copy number variation microarrays. Finally, OGM is compared to amplification-based techniques and a brief outlook for future directions is given.

show abstract

Section: Ogm As a Tool For Detecting Novel Variantsmentioning

confidence: 99%

Optical Genome Mapping for Cytogenetic Diagnostics in AML

Nilius‐Eliliwi

Gerding

Schroers

et al. 2023

Cancers

Self Cite

View full text Add to dashboard Cite

show abstract

“…Based on these data, we recently proposed a next-generation work up applying targeted sequencing and a cytogenomics or structural variant profiling approach [ 5 ]. This approach does not only identify single nucleotide variants addressable for risk stratification or for targeted therapy such as NPM1, IDH1 , or IDH2 .…”

Section: To the Editormentioning

confidence: 99%

Section: To the Editormentioning

confidence: 99%

“…structural variant profiling approach [5]. This approach does not only identify single nucleotide variants addressable for risk stratification or for targeted therapy such as NPM1, IDH1, or IDH2.…”

mentioning

confidence: 99%

“…In an exemplary case, we were able to identify a DDX3X::MLLT10 fusion which might play a causative role in the development of this AML. Additionally, the combination of methods uncovered a genetically biphenotypic disease, which was classified as AML with recurrent genetic aberrations by standard diagnostic procedures [5]. OGM not only detected relevant structural variants in more cases than conventional diagnostics, but also detected additional variants in 27 cases, leading to clarification and redefinition of the karyotype.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Optical Genome Mapping in MDS and AML as tool for structural variant profiling—comment and data update on Yang et al.: “High-resolution structural variant profiling of myelodysplastic syndromes by optical genome mapping uncovers cryptic aberrations of prognostic and therapeutic significance”

et al. 2022

Self Cite

View full text Add to dashboard Cite

Yang et al. recently published their work entitled "High-resolution structural variant profiling of myelodysplastic syndromes by optical genome mapping uncovers cryptic aberrations of prognostic and therapeutic significance" in leukemia [1]. The authors describe a high concordance in 96/99 cases of detected structural variants by routine diagnostics, most importantly chromosomal banding analysis (CBA), and optical genome mapping (OGM) as a whole genome method for structural variant profiling (SVP). More importantly, in 34% of the 101 patients included in the analysis, cryptic variants could be clarified and the risk score according to R-IPSS was changed by additional information obtained by OGM in 17% of patients.These results and the approach chosen are well in line with the data published earlier this year by our group [2]. Although focusing on acute myeloid leukemia (AML), we also included a subgroup of six myelodysplastic syndrome (MDS) patients, three of them with excessive blasts I and three with excessive blasts II, or MDS/AML according to the recently updated international consensus classification [3]. Furthermore, 8 of 21 AML patients had myelodysplasia-related changes.Currently, and updating our previous data, our cohort consists of 42 patients (35 AML and 7 MDS, Table 1). Of 42 patients, a conventional diagnostic approach by cytogenetics (CBA; fluorescence in situ hybridization (FISH) and Copy-number variation (CNV)-microarrays where indicated) was able to detect variants in 26 cases. All but three of these variants could also be seen by OGM, the latter below the applied threshold of 5% variant allele frequency (VAF) and in high-repetitive regions such as around telomers and centromeres [4]. In 27 cases (64%), we could clarify or add additional information by using OGM as a non-DNA dependent amplification based whole genome method. For MDS patients this number was similar with 4/7 cases, where the karyotype could be redefined by utilizing OGM (Table 2).Based on these data, we recently proposed a next-generation work up applying targeted sequencing and a cytogenomics or

show abstract

Proposal of a new genomic framework for categorization of pediatric acute myeloid leukemia associated with prognosis

Umeda

Westover

et al. 2023

Preprint

View full text Add to dashboard Cite

Recent studies on pediatric acute myeloid leukemia (pAML) have revealed pediatric-specific driver alterations, many of which are underrepresented in the current classification schemas. To comprehensively define the genomic landscape of pAML, we systematically categorized 895 pAML into 23 molecular categories that are mutually distinct from one another, including new entities such as UBTF or BCL11B, covering 91.4% of the cohort. These molecular categories were associated with unique expression profiles and mutational patterns. For instance, molecular categories characterized by specific HOXA or HOXB expression signatures showed distinct mutation patterns of RAS pathway genes, FLT3, or WT1, suggesting shared biological mechanisms. We show that molecular categories were strongly associated with clinical outcomes using two independent cohorts, leading to the establishment of a prognostic framework for pAML based on molecular categories and minimal residual disease. Together, this comprehensive diagnostic and prognostic framework forms the basis for future classification of pAML and treatment strategies.

show abstract

Broad genomic workup including optical genome mapping uncovers a DDX3X: MLLT10 gene fusion in acute myeloid leukemia

Cited by 5 publications

References 56 publications

Optical Genome Mapping for Cytogenetic Diagnostics in AML

Optical Genome Mapping for Cytogenetic Diagnostics in AML

Optical Genome Mapping in MDS and AML as tool for structural variant profiling—comment and data update on Yang et al.: “High-resolution structural variant profiling of myelodysplastic syndromes by optical genome mapping uncovers cryptic aberrations of prognostic and therapeutic significance”

Proposal of a new genomic framework for categorization of pediatric acute myeloid leukemia associated with prognosis

Contact Info

Product

Resources

About