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Open Access Research article

Expression of cassini, a murine gamma-satellite sequence conserved in evolution, is regulated in normal and malignant hematopoietic cells

Anna Arutyunyan1, Sonia Stoddart1, Sun-ju Yi1, Fei Fei1, Min Lim1, Paula Groffen2, Niklas Feldhahn13, John Groffen145 and Nora Heisterkamp145*

Author affiliations

1 Section of Molecular Carcinogenesis, Division of Hematology/Oncology and The Saban Research Institute of Children’s Hospital Los Angeles, Los Angeles, CA, 90027, USA

2 Medical Oncology, University Medical Center Groningen, Hanzeplein 1, 9713, GZ, Groningen, The Netherlands

3 Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, 10065, USA

4 Leukemia Research Program, Children’s Hospital Los Angeles, Los Angeles, CA, USA

5 Leukemia and Lymphoma Program, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA

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Citation and License

BMC Genomics 2012, 13:418  doi:10.1186/1471-2164-13-418

Published: 23 August 2012

Abstract

Background

Acute lymphoblastic leukemia (ALL) cells treated with drugs can become drug-tolerant if co-cultured with protective stromal mouse embryonic fibroblasts (MEFs).

Results

We performed transcriptional profiling on these stromal fibroblasts to investigate if they were affected by the presence of drug-treated ALL cells. These mitotically inactivated MEFs showed few changes in gene expression, but a family of sequences of which transcription is significantly increased was identified. A sequence related to this family, which we named cassini, was selected for further characterization. We found that cassini was highly upregulated in drug-treated ALL cells. Analysis of RNAs from different normal mouse tissues showed that cassini expression is highest in spleen and thymus, and can be further enhanced in these organs by exposure of mice to bacterial endotoxin. Heat shock, but not other types of stress, significantly induced the transcription of this locus in ALL cells. Transient overexpression of cassini in human 293 embryonic kidney cells did not increase the cytotoxic or cytostatic effects of chemotherapeutic drugs but provided some protection. Database searches revealed that sequences highly homologous to cassini are present in rodents, apicomplexans, flatworms and primates, indicating that they are conserved in evolution. Moreover, CASSINI RNA was induced in human ALL cells treated with vincristine. Surprisingly, cassini belongs to the previously reported murine family of γ-satellite/major satellite DNA sequences, which were not known to be present in other species.

Conclusions

Our results show that the transcription of at least one member of these sequences is regulated, suggesting that this has a function in normal and transformed immune cells. Expression of these sequences may protect cells when they are exposed to specific stress stimuli.

Keywords:
Murine γ-satellite DNA; Major mouse satellite; Pericentromeric; Acute lymphoblastic leukemia; MEFs; Nilotinib; Stress; Cytotoxic drugs