Case Report: The First Report of NUP214-ABL1 Fusion Gene in Acute Myeloid Leukemia Patient Detected by Next-Generation Sequencing

Wang, Huanping; He, Jun-Jun; Zhu, Qiaoyun; Wang, Lin; Jian-hu, LI; Huang, Jiansong; Xie, Wanzhuo; Zhu, Hong‐Hu; Jin, Jie

doi:10.3389/fonc.2021.706798

Cited by 5 publications

(4 citation statements)

References 16 publications

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“…as it was seen in this case with a normal karyotype. There was one case in literature showing an AML patient with this fusion, who was treated with conventional chemotherapy for AML [43]. This was the second published case with this fusion in AML [44].…”

Section: Discussionmentioning

confidence: 89%

Challenges in accuracy in molecular genetic diagnosis of childhood AML: case series

Mota,

de Toledo,

Tesser-Gamba

et al. 2024

Preprint

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Survival rate of children with Acute Myeloid Leukemia (AML) improves gradually through cooperative studies. However, the outcome depends on heterogeneous mechanisms. Comprehending the genetic background of pediatric Acute Myeloid Leukemia (AML) is the key to risk stratification. Next Generation Sequencing (NGS) technology uses target panels that may detect additional genetic subsets. The study describes the experience of using NGS for treating pediatric AML patients at an institution. Patients who showed poor outcome aberration were referred to hematopoietic stem cell transplant (HSCT). 11 patients were tested. Aberrations were found in all subjects, mainly only in the NGS panel, indicating referral to HSCT in first remission in 2 cases and helping to outline the genetic features in all cases. The availability of NGS resources has had a therapeutic impact. NGS helped outline the patients' genetic features and decision for HSCT. NGS is a valuable tool in the precision medicine era and should be widely accessible.

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Section: Discussionmentioning

confidence: 89%

Challenges in accuracy in molecular genetic diagnosis of childhood AML: case series

Mota,

de Toledo,

Tesser-Gamba

et al. 2024

Preprint

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“…The NUP214::ABL1 -positive cases included two patients with AML patients. To our knowledge, only one case of NUP214:: ABL1 -positive AML has been reported [ 13 ], making our patients the second and third cases reported to date. Case 8 was referred to our hospital in 2017 after having been diagnosed with myeloid leukemia associated with Down syndrome.…”

Section: Discussionmentioning

confidence: 98%

“…SET::NUP214 is frequently observed in T-cell acute lymphoblastic leukemia (T-ALL) but rarely in AML or acute undifferentiated leukemia (AUL) [ 8 - 11 ]. NUP214::ABL1 is detected in up to 6% of T-ALL patients, and only one case in AML has been reported to date [ 12 , 13 ]. DEK::NUP214 is involved in 1% of AML and myelodysplastic syndromes [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

NUP214 Rearrangements in Leukemia Patients: A Case Series From a Single Institution

Choi,

Min,

Lee

et al. 2023

Ann Lab Med

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Background: The three best-known NUP214 rearrangements found in leukemia (SET:: NUP214, NUP214::ABL1, and DEK::NUP214) are associated with treatment resistance and poor prognosis. Mouse experiments have shown that NUP214 rearrangements alone are insufficient for leukemogenesis; therefore, the identification of concurrent mutations is important for accurate assessment and tailored patient management. Here, we characterized the demographic characteristics and concurrent mutations in patients harboring NUP214 rearrangements.Methods: To identify patients with NUP214 rearrangements, RNA-sequencing results of diagnostic bone marrow aspirates were retrospectively studied. Concurrent targeted nextgeneration sequencing results, patient demographics, karyotypes, and flow cytometry information were also reviewed.Results: In total, 11 patients harboring NUP214 rearrangements were identified, among whom four had SET::NUP214, three had DEK::NUP214, and four had NUP214::ABL1. All DEK::NUP214-positive patients were diagnosed as having AML. In patients carrying SET::NUP214 and NUP214::ABL1, T-lymphoblastic leukemia was the most common diagnosis (50%, 4/8). Concurrent gene mutations were found in all cases. PFH6 mutations were the most common (45.5%, 5/11), followed by WT1 (27.3%, 3/11), NOTCH1 (27.3%, 3/11), FLT3-internal tandem duplication (27.3%, 3/11), NRAS (18.2%, 2/11), and EZH2 (18.2%, 2/11) mutations. Two patients represented the second and third reported cases of NUP214::ABL1-positive AML. Conclusions:We examined the characteristics and concurrent test results, including gene mutations, of 11 leukemia patients with NUP214 rearrangement. We hope that the elucidation of the context in which they occurred will aid future research on tailored monitoring and treatment.

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“…In terms of gene fusions, the current NGS assay can detect various common hybrid fusion transcripts in a single reaction, as well as identify rare/novel hybrid fusion transcripts and clarify fusion partner genes, when cytogenetics/FISH may be limited/cryptic (e.g., NUP214:: ABL1 [34][35][36][37][38][39][40][41][42]). Also, by defining the exons involved in a fusion, this assay can inform appropriate exon-specific assay design for follow-up MRD testing by other methods (e.g., qRT-PCR), which are required since the analytical sensitivity (i.e., limit of detection) of this NGS assay for fusions is not adequate for MRD.…”

Section: Discussionmentioning

confidence: 99%

Detection of Hybrid Fusion Transcripts, Aberrant Transcript Expression, and Specific Single Nucleotide Variants in Acute Leukemia and Myeloid Disorders with Recurrent Gene Rearrangements

Li¹,

Deng²,

Kaner³

et al. 2023

Pathobiology

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Introduction: A variety of gene rearrangements and molecular alterations are key drivers in the pathobiology of acute leukemia and myeloid disorders; current classification systems increasingly incorporate these findings in diagnostic algorithms. Therefore, clinical laboratories require versatile tools, which can detect an increasing number and variety of molecular and cytogenetic alterations of clinical significance. Methods: We validated an RNA-based NGS assay that enables the detection of: i) numerous hybrid fusion transcripts (including rare/novel gene partners), ii) aberrantly expressed EVI1(MECOM) and IKZF1 (Del Exons 4-7) transcripts, and iii) hotspot variants in KIT, ABL1, NPM1 (relevant in the context of gene rearrangement status). Results: For hybrid fusion transcripts, the assay showed 98-100% concordance for known positive and negative samples, with an analytical sensitivity (ie, limit of detection) of approximately 0.8% cells. Cases with underlying EVI1 (MECOM) translocations demonstrated increased EVI1(MECOM) expression. Aberrant IKZF1 (Del Exons 4-7) transcripts detectable with the assay were also present on orthogonal RT-PCR. Specific hotspot mutations in KIT, ABL1 and NPM1 detected with the assay showed 100% concordance with orthogonal testing. Lastly, several illustrative cases are included to highlight the assay’s clinically relevant contributions to patient work-up. Discussion/Conclusion: Through its ability to simultaneously detect various gene rearrangements, aberrantly expressed transcripts and hotspot mutations, this RNA-based NGS assay is a valuable tool for clinical laboratories to supplement other molecular and cytogenetic methods used in the diagnostic workup, and in clinical research, for patients with acute leukemia and myeloid disorders.

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Case Report: The First Report of NUP214-ABL1 Fusion Gene in Acute Myeloid Leukemia Patient Detected by Next-Generation Sequencing

Cited by 5 publications

References 16 publications

Challenges in accuracy in molecular genetic diagnosis of childhood AML: case series

Challenges in accuracy in molecular genetic diagnosis of childhood AML: case series

NUP214 Rearrangements in Leukemia Patients: A Case Series From a Single Institution

Detection of Hybrid Fusion Transcripts, Aberrant Transcript Expression, and Specific Single Nucleotide Variants in Acute Leukemia and Myeloid Disorders with Recurrent Gene Rearrangements

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