Fusion of the genes ataxin 2 like,<i>ATXN2L</i>, and Janus kinase 2,<i>JAK2</i>, in cutaneous CD4 positive T-cell lymphoma

Panagopoulos, Ioannis; Gorunova, Ludmila; Spetalen, Signe; Bassarova, Assia; Beiske, Klaus; Micci, Francesca; Heim, Sverre

doi:10.18632/oncotarget.21790

Cited by 18 publications

(15 citation statements)

References 37 publications

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“…Recently, ataxin-2-like (ATXN2L) was discovered as a novel regulator of SG 6 . It was reported that ATXN2L was widely expressed in immortalized cell lines, and ATXN2L-JAK2 fusion was found in CD4-positive T-cell lymphoma 8 . ATXN2L is a paralog of Ataxin-2 (ATXN2) but without abnormal polyQ expended track, which is conserved in most of the ATXNs and drives the pathogenesis of neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

ATXN2L upregulated by epidermal growth factor promotes gastric cancer cell invasiveness and oxaliplatin resistance

Pan

et al. 2019

Cell Death Dis

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For gastric cancer (GC) control, metastasis and chemoresistance are the major challenges, accompanied with various stresses. Ataxin-2-like (ATXN2L) was discovered as a novel regulator of stress granules, yet its function in cancers remained unknown. Hence, we wanted to explore the functions of ATXN2L to see whether it participates in stress-related cancer malignant activities. Clinical follow-up was performed to see the impact of ATXN2L on GC patient survival. As a result, ATXN2L expression was upregulated in GC tissue and indicated adverse prognosis for overall survival and recurrence. In GC cells, ATXN2L expression was knocked down and functional experiments were performed. ATXN2L promoted GC cell migration and invasion via epithelial to mesenchymal transition, yet no influence on proliferation was detected by ATXN2L interference. When adding the chemotherapeutic agent oxaliplatin to induce stress, silencing ATXN2L sensitized GC cells to oxaliplatin. Interestingly, oxaliplatin was found to in turn promote ATXN2L expression and stress granule assembly. Then, two acquired oxaliplatin-resistant strains were generated by long-term oxaliplatin induction. The oxaliplatin-resistant strains presented with elevated ATXN2L levels, while silencing ATXN2L in the strains reversed the oxaliplatin resistance by increasing reactive oxygen species production and apoptosis. These results suggested that ATXN2L was responsible for not only intrinsic but also acquired oxaliplatin chemoresistance. Finally, ATXN2L-related signaling was screened using bioinformatic methods, and epidermal growth factor (EGF) was verified to promote ATXN2L expression via PI3K/Akt signaling activation. Blocking EGFR/ATXN2L signaling reversed GC cell oxaliplatin resistance and inhibited migration. In conclusion, ATXN2L promotes cell invasiveness and oxaliplatin resistance and can be upregulated by EGF via PI3K/Akt signaling. ATXN2L may be an indicator and therapeutic target in GC, especially for oxaliplatin-based chemotherapy.

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Section: Introductionmentioning

confidence: 99%

ATXN2L upregulated by epidermal growth factor promotes gastric cancer cell invasiveness and oxaliplatin resistance

Pan

et al. 2019

Cell Death Dis

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“…RNA sequencing was performed as described in detail previously [ 11 ]. Total RNA was extracted from the patient´s bone marrow cells at the time of secondary MDS diagnosis using miRNeasy Mini Kit (Qiagen Nordic, Oslo, Norway) and one μg was sent to the Genomics Core Facility at the Norwegian Radium Hospital, Oslo University Hospital ( http://genomics.no/oslo/ ) for high-throughput paired-end RNAsequencing.…”

Section: Methodsmentioning

confidence: 99%

RUNX1-PDCD6 fusion resulting from a novel t(5;21)(p15;q22) chromosome translocation in myelodysplastic syndrome secondary to chronic lymphocytic leukemia

et al. 2018

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Leukemic cells often carry chromosome aberrations which generate chimeric genes of pathogenetic, diagnostic, and prognostic importance. New rearrangements giving rise to novel fusion genes define hitherto unrecognized genetic leukemia subgroups. G-banding, fluorescence in situ hybridization (FISH), and molecular genetic analyses were done on bone marrow cells from a patient with chronic lymphocytic leukemia (CLL) and secondary myelodysplasia. The G-banding analysis revealed the karyotype 46,XX,del(21)(q22)[9]/46,XX[2]. FISH on metaphase spreads with a RUNX1 break apart probe demonstrated that part of RUNX1 (from 21q22) had moved to chromosome band 5p15. RNA sequencing showed in-frame fusion of RUNX1 with PDCD6 (from 5p15), something that was verified by RT-PCR together with Sanger sequencing. Further FISH analyses with PDCD6 and RUNX1 home-made break apart/double fusion probes showed a red signal (PDCD6) on chromosome 5, a green signal on chromosome 21 (RUNX1), and two yellow fusion signals, one on der(5) and the other on der(21). Reassessment of the G-banding preparations in light of the FISH and RNA-sequencing data thus yielded the karyotype 46,XX,t(5;21)(p15;q22)[9]/46,XX[2]. The t(5;21)(p15;q22)/RUNX1-PDCD6 was detected only by performing molecular studies of the leukemic cells, but should be sought after also in other leukemic/myelodysplastic cases with del(21q).

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“…These techniques have impacted every field of molecular research, escalating previously used sequencing technologies [ 11 ], and opening the way to the -omic sciences foundation [ 1 , 2 ]. Indeed, NGS methods allow the sequencing of entire genomes [ 12 , 13 , 14 , 15 ], of exomes [ 16 , 17 , 18 ], of panels of genes related to a disease of interest [ 19 , 20 , 21 ], or of a single gene [ 22 , 23 , 24 , 25 , 26 ], but can also be used to explore the entire transcriptome [ 27 , 28 , 29 ], small RNAs [ 30 , 31 , 32 ], the epigenome [ 33 , 34 ], and the microbiome [ 35 , 36 , 37 , 38 ].…”

Section: High-throughput Analysesmentioning

confidence: 99%

“…In addition to the study of sequence variations at the DNA level, NGS methods can be used to study genetic variability, and the mechanisms underlying the onset of specific diseases at epigenetic, transcriptomic and metagenomic levels [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. Indeed, several factors, other than individual genetic predisposition, such as diet, environmental factors and lifestyle, can influence the epigenome, the transcriptome and the microbiome [ 2 , 50 ].…”

Section: High-throughput Analysesmentioning

confidence: 99%

“…In the case of RNA studies for example, NGS-based approaches have overcome the use of microarrays: NGS allows the analysis of virtually all the RNA molecules, known and unknown, present in a sample, at a lower cost [ 2 , 7 ]. In addition, alternative splicing isoforms and long non-coding RNAs can also be highlighted [ 2 , 7 , 27 , 28 , 29 ], and specific small RNA classes can be enriched and sequenced [ 30 , 31 , 32 ]. Finally, recent applications are also showing the potential of NGS for single cells RNA sequencing [ 51 , 52 ].…”

Section: High-throughput Analysesmentioning

confidence: 99%

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The High-Throughput Analyses Era: Are We Ready for the Data Struggle?

D’Argenio

2018

High-Throughput

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Recent and rapid technological advances in molecular sciences have dramatically increased the ability to carry out high-throughput studies characterized by big data production. This, in turn, led to the consequent negative effect of highlighting the presence of a gap between data yield and their analysis. Indeed, big data management is becoming an increasingly important aspect of many fields of molecular research including the study of human diseases. Now, the challenge is to identify, within the huge amount of data obtained, that which is of clinical relevance. In this context, issues related to data interpretation, sharing and storage need to be assessed and standardized. Once this is achieved, the integration of data from different -omic approaches will improve the diagnosis, monitoring and therapy of diseases by allowing the identification of novel, potentially actionably biomarkers in view of personalized medicine.

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Fusion of the genes ataxin 2 like,ATXN2L, and Janus kinase 2,JAK2, in cutaneous CD4 positive T-cell lymphoma

Cited by 18 publications

References 37 publications

ATXN2L upregulated by epidermal growth factor promotes gastric cancer cell invasiveness and oxaliplatin resistance

ATXN2L upregulated by epidermal growth factor promotes gastric cancer cell invasiveness and oxaliplatin resistance

RUNX1-PDCD6 fusion resulting from a novel t(5;21)(p15;q22) chromosome translocation in myelodysplastic syndrome secondary to chronic lymphocytic leukemia

The High-Throughput Analyses Era: Are We Ready for the Data Struggle?

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