Case report: Exome sequencing identifies T-ALL with myeloid features as a IKZF1-struck early precursor T-cell malignancy

Hansen, Mette Halskov; Nederby, Line; Kjeldsen, Eigil; Petersen, Marianne A; Ommen, Hans Beier; Hokland, Peter

doi:10.1016/j.lrr.2017.11.002

Cited by 4 publications

(4 citation statements)

References 18 publications

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“…This patient was devoid of malignant cells in CSF at CNS relapse and did not harbor a chromosome 1q loss or gain in the investigated materials. The WES copy-number profiling was based on the detection of allelic imbalances by variant allele frequencies and relative read-depth ratios, as previously implemented in the molecular profiling of four other patients with MCL using WES [6] (see also [7] and [5] ), with the exception that the coverage of chromosome 1p arm was used for internal confirmation of the 1q copy number alteration, and to circumvent sequencing batch effects. All read depth ratios were normalized to that of the respective paired control.…”

Section: Discussionmentioning

confidence: 99%

Distal chromosome 1q aberrations and initial response to ibrutinib in central nervous system relapsed mantle cell lymphoma

Hansen

Juul‐Jensen

Cédile

et al. 2021

Leukemia Research Reports

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Relapse involving the central nervous system (CNS) is an infrequent event in the progression of mantle cell lymphoma (MCL) with an incidence of approximately four percent. We report four cases of MCL with CNS relapse. In three of the four patients a large chromosomal copy-number alteration (CNA) of 1q was demonstrated together with TP53 mutation/deletion. These patients experienced brief response to ibrutinib, whereas a fourth patient harboring mutated ATM demonstrated a long-term effect to ibrutinib and no CNA. Although it is unclear whether chromosome 1q CNA contribute to specific phenotypes these reports may be of value as such lesions are uncommon features of MCL.

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Section: Discussionmentioning

confidence: 99%

Distal chromosome 1q aberrations and initial response to ibrutinib in central nervous system relapsed mantle cell lymphoma

Hansen

Juul‐Jensen

Cédile

et al. 2021

Leukemia Research Reports

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“…If one gene were to capture the ambiguous nature of the neoplasms derived from B‐ and T‐lineage lymphoid precursors, the Ikaros transcription factor IKZF1 is a strong candidate for such a gene, as it is a master regulator of lymphocyte differentiation . Although primarily recognized for its role in B‐ALL (Marke et al , ), growing evidence supports that IKZF1 plays a cardinal role in ETP‐ALL (Zhang et al , ; Hansen et al , ). Additionally, germline variants have been investigated in the predisposition of developing childhood acute lymphoblastic leukemia (Churchman et al , ).…”

Section: Some Major Contributions In Genomic Profiling Of the Lymphoimentioning

confidence: 99%

A decade with whole exome sequencing in haematology

2019

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The first decade of capture-based targeted whole exome sequencing (WES) has now passed, while the sequencing modality continues to find more widespread usage in clinical research laboratories and still offers an unprecedented diagnostic assay in terms of throughput, informational content and running costs. Until quite recently, WES has been out of reach for many clinicians and molecular biologists, and it still poses issues or is met with some reluctance with regards to cost versus benefit in terms of effective assay costs, hands-on laboratory work and data analysis bottlenecks. Although WES is used more than ever, it may also be argued that the usage is peaking and that new implementations, or relevance in its current state, will likely be leveling off during the following decade as the price on whole genome sequencing continues to drop. In this review, we focus on the past decade of targeted whole exome sequencing in malignant hematology. We thematically revisit some of the significant discoveries and niches that use next-generation sequencing, and we outline what and how WES has contributed to the fieldfrom clonal hematopoiesis of the aging bone marrow to profiling malignancies down to the single cell.

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“…That single cell studies can still lead to novel observations in AML is evidenced by a recent report, which revealed a surprising heterogeneity in the response to a FLT3 tyrosine kinase inhibitor at the single cell level (Smith et al, 2017). This contrasts to bulk analyses, which depends on some computational generalisations in order to establish mutational or coarse clonal frequencies (Hansen et al, 2018). As might be envisaged, such assays entail considerable efforts if single cells are to be obtained by classical methods, such as fluorescence-activated cell sorting (FACS).…”

Section: Deconstruction Of the Lsc Population Down To The Single Cellmentioning

confidence: 99%

The concept of leukaemic stem cells in acute myeloid leukaemia 25 years on: hitting a moving target

et al. 2019

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Summary The concept of leukaemic stem cells (LSCs) was experimentally suggested 25 years ago through seminal data from John Dick's group, who showed that a small fraction of cells from acute myeloid leukaemia (AML) patients were able to be adoptively transferred into immunodeficient mice. The initial estimation of the frequency was 1:250 000 leukaemic cells, clearly indicating the difficulties ahead in translating knowledge on LSCs to the clinical setting. However, the field has steadily grown in interest, expanse and importance, concomitantly with the realisation of the molecular background for AML culminating in the sequencing of hundreds of AML genomes. The literature is now ripe with contributions describing how different molecular aberrations are more or less specific for LSCs, as well as reports showing selectivity in targeting LSCs in comparison to normal haematopoietic stem and progenitor cells. However, we argue here that these important data have not yet been fully realised within the clinical setting. In this clinically focused review, we outline the difficulties in identifying and defining LSCs at the individual patient level, with special emphasis on intraclonal heterogeneity. In addition, we suggest areas of future focus in order to realise the concept as real‐time benefit for AML patients.

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Case report: Exome sequencing identifies T-ALL with myeloid features as a IKZF1-struck early precursor T-cell malignancy

Cited by 4 publications

References 18 publications

Distal chromosome 1q aberrations and initial response to ibrutinib in central nervous system relapsed mantle cell lymphoma

Distal chromosome 1q aberrations and initial response to ibrutinib in central nervous system relapsed mantle cell lymphoma

A decade with whole exome sequencing in haematology

The concept of leukaemic stem cells in acute myeloid leukaemia 25 years on: hitting a moving target

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