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Updated: Jul 10, 2026

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Published on: November 10, 2017
Amplification at 7q22 targets cyclin-dependent kinase 6 in T-cell lymphoma
S Nagel1, E Leich, H Quentmeier
1Department of Human and Animal Cell Cultures, DSMZ, Braunschweig, Germany. sna@dsmz.de
Abstract:
Recurrent chromosomal aberrations in hematopoietic tumors target genes involved in pathogenesis. Their identification and functional characterization are therefore important for the establishment of rational therapies. Here, we investigated genomic amplification at 7q22 in the T-cell lymphoma cell line SU-DHL-1 belonging to the subtype of anaplastic large-cell lymphoma (ALCL). Cytogenetic analysis mapped this amplicon to 86-95 Mb. Copy-number determination quantified the amplification level at 5- to 6-fold. Expression analysis of genes located within this region identified cyclin-dependent kinase 6 (CDK6) as a potential amplification target. In comparison with control cell lines, SU-DHL-1 expressed considerably higher levels of CDK6. Functionally, SU-DHL-1 cells exhibited reduced sensitivity to rapamycin treatment, as indicated by cell growth and cell cycle analysis. Rapamycin reportedly inhibits degradation of the CDK inhibitor p27 with concomitant downregulation of cyclin D3, implying a proliferative advantage for CDK6 overexpression. Amplification of the CDK6 locus was analyzed in primary T-cell lymphoma samples and, while detected infrequently in those classified as ALCL (1%), was detected in 23% of peripheral T-cell lymphomas not otherwise specified. Taken together, analysis of the 7q22 amplicon identified CDK6 as an important cell cycle regulator in T-cell lymphomas, representing a novel potential target for rational therapy.
Insights
Genomic amplification of CDK6 in T-cell lymphoma drives cell proliferation. This finding identifies CDK6 as a potential therapeutic target for T-cell lymphomas, offering new avenues for rational treatment strategies.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Recurrent chromosomal aberrations are key drivers in hematopoietic tumors.
- Identifying and functionally characterizing these aberrations is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the genomic amplification at 7q22 in anaplastic large-cell lymphoma (ALCL) cell line SU-DHL-1.
- To identify and functionally characterize the target genes within this amplified region, specifically focusing on their role in T-cell lymphoma pathogenesis.
Main Methods:
- Cytogenetic analysis to map the amplicon region.
- Copy-number determination to quantify amplification levels.
- Gene expression analysis to identify potential targets.
- Cellular assays (growth, cell cycle) to assess functional impact.
- Analysis of primary T-cell lymphoma samples for amplification frequency.
Main Results:
- A 5- to 6-fold genomic amplification at 7q22 was identified in SU-DHL-1 cells.
- Cyclin-dependent kinase 6 (CDK6) was identified as a highly expressed gene within the amplified region.
- SU-DHL-1 cells showed reduced sensitivity to rapamycin, consistent with CDK6 overexpression.
- CDK6 locus amplification was found in 23% of peripheral T-cell lymphomas not otherwise specified, but rarely in ALCL (1%).
Conclusions:
- The 7q22 amplicon targets CDK6, a critical cell cycle regulator in T-cell lymphomas.
- CDK6 overexpression confers a proliferative advantage and impacts drug sensitivity.
- CDK6 represents a novel and promising therapeutic target for T-cell lymphomas.
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