Loss of Irreversibility of Granulocytic Differentiation Induced by Dimethyl Sulfoxide in HL-60 Sublines with a Homogeneously Staining Region

Kitajima, Kenji; Haque, Masudul; Nakamura, Hitoshi; Hirano, Tetsuo; Utiyama, Hiroyasu

doi:10.1006/bbrc.2001.5892

Cited by 12 publications

(13 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our working hypothesis was based on several lines of evidence: the human leukemia cell line HL-60 harbors MYC amplification in the form of dmins during early passages that are then replaced by HSRs during continuous long-term culture (6). In HL-60 cells treated with DMSO, granulocyte differentiation is induced in cells with either dmins or HSRs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Does MYCN Amplification Manifested as Homogeneously Staining Regions at Diagnosis Predict a Worse Outcome in Children with Neuroblastoma? A Children's Oncology Group Study

Moreau

McGrady²,

London³

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: MYCN amplification in neuroblastoma tumor cells is manifested primarily as double minutes (dmins), whereas in cell lines it often appears in the form of homogeneously staining regions (HSR), suggesting that HSRs are associated with a more aggressive tumor phenotype and worse clinical outcome. The aim of this study was to determine whether children with neuroblastoma in which MYCN oncogene amplification is manifested as HSRs at diagnosis have a worse prognosis than those whose tumors exhibit dmins. Experimental Design: A retrospective analysis of primary neuroblastomas analyzed for MYCN amplification by the Children's Oncology Group between 1993 and 2004 was done. Tumors with MYCN amplification were defined as having dmins, HSRs, or both (dmins + HSRs), and associations with currently used risk group stratification variables and patient outcome were assessed. Results: Of the 4,102 tumor samples analyzed, 800 (19.5%) had MYCN amplification. Among the 677 tumors for which the pattern of amplification was known, 629 (92.9%) had dmins, 40 (5.9%) had HSRs, and 8 (0.1%) had dmins + HSRs. Although MYCN amplification is associated with older age, higher stage, and unfavorable histology, whether the amplification occurred as dmins or HSRs did not significantly affect these risk factors. There were no differences in the event-free survival (EFS) or overall survival in patients with MYCN amplification manifested as either dmins or HSRs (5-year EFS, 35 F 3% versus 38 F 15%; P = 0.59). Although the eight patients with dmins + HSRs fared worse than either of the individual subgroups (EFS, 18 F 16% versus 35 F 3% for dmins and 38 F 15% for HSRs), these differences were not significant. Conclusions: MYCN amplification in any form (HSRs or dmins) is associated with a poor outcome.DNA amplification is a mechanism by which a cancer cell acquires multiple copies of part of its genome, enabling it to overexpress oncogenes that confer a selective growth advantage or to acquire resistance to chemotherapeutic agents (1, 2).Gene amplification is most often manifested as paired extrachromosomal self-replicating double-minute chromatin bodies (dmins), which are acentric and atelomeric (3), or as uniformly staining, linearly integrated chromosomal segments called homogenously staining regions (HSR; ref. 4). dmins are commonly seen in primary tumors, whereas HSRs tend to predominate in cultured neoplastic cells (5, 6). HSRs are thought to be formed by integration of multimerized sequences of dmins into chromosomes (7,8). They are considered stable forms of amplification because they provide a faithful mechanism by which the extra copies of the gene can be passed onto the daughter cells. dmins, on the other hand, are considered highly unstable, as they tend to be lost over time either by micronucleation or by uneven distribution into daughter cells (2, 9). The transition from dmins to HSRs is thought to occur through stepwise selection that confers on cells a selective growth advantage, enabling them to survive in culture th...

show abstract

Section: Discussionmentioning

confidence: 99%

“…4). dmins are commonly seen in primary tumors, whereas HSRs tend to predominate in cultured neoplastic cells (5,6). HSRs are thought to be formed by integration of multimerized sequences of dmins into chromosomes (7,8).…”

mentioning

confidence: 99%

Does MYCN Amplification Manifested as Homogeneously Staining Regions at Diagnosis Predict a Worse Outcome in Children with Neuroblastoma? A Children's Oncology Group Study

Moreau

McGrady²,

London³

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Some types of cancer cell respond to the anticancer drug hydroxyurea by excluding unstable extrachromosomal elements, which then lose their proliferative nature. In HL-60 cells, the original MYC genetic locus remained intact after dmin was excluded, but was no longer transcribed (36). These observations suggest that the expression of genes from dmin, with its altered DNA structure, and from the intact chromosome are different, and can be interpreted as being due to aberrant gene expression from dmin (including the MYC oncogene).…”

Section: Aml and Ccdc26mentioning

confidence: 94%

“…It is well known that genes located in extrachromosomal elements such as dmin are actively transcribed, but the mechanism behind this phenomenon is not well understood (60,61). Differences between dmin and an intact chromosome are caused by differences in chromatin structure, which is indicated by differences in DNase I hypersensitivity (36). Similarly to other gene silencing lncRNAs, an ncRNA encoded by the CCDC26 locus might suppress the expression of other nearby genes.…”

Section: Overview Of the Ccdc26 Genetic Locusmentioning

confidence: 99%

Is CCDC26 a Novel Cancer-Associated Long-Chain Non-Coding RNA?

Hirano¹

2013

Oncogene and Cancer - From Bench to Clinic

Self Cite

View full text Add to dashboard Cite

“…The anticancer drug hydroxyurea blocks proliferation of HL-60 cells by promoting exclusion of dmins. Even after exclusion of dmins, MYC of the original chromosomal locus remained intact, but was no longer transcribed [58] . These observations suggest aberrant gene(s) on dmins other than MYC might be responsible for proliferation of HL-60 cells.…”

Section: Ccdc26 In Acute Myeloid Leukemiamentioning

confidence: 99%

The role of the CCDC26 long noncoding RNA as a tumor suppressor

Hirano

2015

RNA Dis

View full text Add to dashboard Cite

CCDC26 on chromosome 8q24 is considered to encode a long intergenic noncoding RNA because the short open reading frame within the mRNA transcribed from this gene is not conserved in any other species. Genome-wide analysis has revealed association of CCDC26 with certain tumors, for instance low-level glioma. Moreover, moderate amplifications of the whole or part of the CCDC26 genetic locus have been observed in pediatric acute myeloid leukemia patients. The CCDC26 gene is amplified in the HL-60 acute myeloid leukemia cell line, in which double minute chromosomes-abnormal tiny chromosomes-harbor the CCDC26 gene. We examined the function of CCDC26 by gene knock-down (KD) using short hairpin RNAs in K562 human myeloid leukemia cells. In four stable KD clones, CCDC26 expression was suppressed to 1% of its normal level by transcriptional gene suppression, not post-transcriptional suppression. The growth rates of these KD clones were reduced compared with those of control cells in media containing high serum concentrations. In contrast, in media containing much lower serum concentrations, the KD clones exhibited significantly higher growth rates than controls, and increased survival after serum withdrawal. Enhanced expression of a receptor tyrosine kinase, KIT, was detected in the KD clones, and treatment with ISCK03, a KIT inhibitor, eliminated their increased survival in the absence of serum. Therefore, CCDC26 seems to control myeloid leukemia cell growth through regulation of KIT expression. These observations suggest that CCDC26 is a tumor-suppressive long noncoding RNA because it suppresses the KIT oncogene that supports survival of cancer cells in the stem cell state.

show abstract

Loss of Irreversibility of Granulocytic Differentiation Induced by Dimethyl Sulfoxide in HL-60 Sublines with a Homogeneously Staining Region

Cited by 12 publications

References 29 publications

Does MYCN Amplification Manifested as Homogeneously Staining Regions at Diagnosis Predict a Worse Outcome in Children with Neuroblastoma? A Children's Oncology Group Study

Does MYCN Amplification Manifested as Homogeneously Staining Regions at Diagnosis Predict a Worse Outcome in Children with Neuroblastoma? A Children's Oncology Group Study

Is CCDC26 a Novel Cancer-Associated Long-Chain Non-Coding RNA?

The role of the CCDC26 long noncoding RNA as a tumor suppressor

Contact Info

Product

Resources

About