DNA microarray analysis of stage progression mechanism in myelodysplastic syndrome

Ueda, Masuzu; Ota, Jun; Yamashita, Yuichi; Choi, Young Lim; Ohki, Ruri; Wada, Toyoji; Koinuma, Koji; Kano, Yasuhiko; Ozawa, Keiya; Mano, Hiroyuki

doi:10.1046/j.1365-2141.2003.04601.x

Cited by 61 publications

(43 citation statements)

References 25 publications

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“…PIASy was shown to be hypermethylated in patients with MDS-derived AML (see above) [60]. We could not find any reports on PIAS hypermethylation in de novo AML.…”

Section: Hypermethylation Of Stat Inhibitors In Acute Leukemiascontrasting

confidence: 41%

“…However, SOCS1 hypermethylation was detected in MDS patient samples [58,59]. Finally, PIASy mRNA was studied in blasts from 37 patients; it was present in stem cells from 13 MDS patients in the early phase (refractory anemia) of the disease but its expression was suppressed in samples from patients in the more advanced stages (nine with refractory anemia with excess of blasts and 13 MDS associated leukemia) of the disease [60] to suggest that methylation of STAT regulators may be involved in the transformation of MDS to AML.…”

Section: Hypermethylation Of Stat Inhibitors In Myelodysplastic Syndrmentioning

confidence: 99%

“…We could not find any reports on PIAS hypermethylation in de novo AML. Interestingly, overexpression of PIASy resulted in growth suppression in a myeloid leukemia cell line model [60].…”

Section: Hypermethylation Of Stat Inhibitors In Acute Leukemiasmentioning

confidence: 99%

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Epigenetic regulation of signal transducer and activator of transcription 3 in acute myeloid leukemia

2008

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We have demonstrated that constitutive signal transducer and activator of transcription (STAT) 3 activity, observed in approximately 50% of acute myeloid leukemia (AML) cases, is associated with adverse treatment outcome. Constitutive STAT3 activation may result from the expression of oncogenic protein tyrosine kinases or from autocrine stimulation by hematopoietic growth factors. These causes are generally neither necessary nor sufficient for leukemogenesis; additional transforming events or growth stimulatory processes are needed. Here we review the literature addressing epigenetic regulation as a mechanism controlling STAT3 signaling in AML. A better understanding of mechanisms of dysregulation of STAT signaling pathways may serve as a basis for designing novel therapeutic strategies that target these pathways in leukemia cells.

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“…PIASy was shown to be hypermethylated in patients with MDS-derived AML (see above) [60]. We could not find any reports on PIAS hypermethylation in de novo AML.…”

Section: Hypermethylation Of Stat Inhibitors In Acute Leukemiascontrasting

confidence: 41%

Section: Hypermethylation Of Stat Inhibitors In Myelodysplastic Syndrmentioning

confidence: 99%

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Epigenetic regulation of signal transducer and activator of transcription 3 in acute myeloid leukemia

2008

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“…Examining gene expression profiles has been extremely useful for establishing different phenotypes in cancer. [1][2][3] Various microarray profiles in mood disorder have been reported that use different microarray platforms, analysis methodology, regional differences, agonal factors and brain pH. [4][5][6][7][8][9][10][11][12][13][14] Presumably, a substantial heterogeneity in the pathophysiology of mood disorder coupled with small sample sizes and small fold changes contributes to the lack of consistency among the findings.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Mitochondrial-related gene expression changes are sensitive to agonal-pH state: implications for brain disorders

et al. 2006

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Mitochondrial defects in gene expression have been implicated in the pathophysiology of bipolar disorder and schizophrenia. We have now contrasted control brains with low pH versus high pH and showed that 28% of genes in mitochondrial-related pathways meet criteria for differential expression. A majority of genes in the mitochondrial, chaperone and proteasome pathways of nuclear DNA-encoded gene expression were decreased with decreased brain pH, whereas a majority of genes in the apoptotic and reactive oxygen stress pathways showed an increased gene expression with a decreased brain pH. There was a significant increase in mitochondrial DNA copy number and mitochondrial DNA gene expression with increased agonal duration. To minimize effects of agonal-pH state on mood disorder comparisons, two classic approaches were used, removing all subjects with low pH and agonal factors from analysis, or grouping low and high pH as a separate variable. Three groups of potential candidate genes emerged that may be mood disorder related: (a) genes that showed no sensitivity to pH but were differentially expressed in bipolar disorder or major depressive disorder; (b) genes that were altered by agonal-pH in one direction but altered in mood disorder in the opposite direction to agonal-pH and (c) genes with agonal-pH sensitivity that displayed the same direction of changes in mood disorder. Genes from these categories such as NR4A1 and HSPA2 were confirmed with Q-PCR. The interpretation of postmortem brain studies involving broad mitochondrial gene expression and related pathway alterations must be monitored against the strong effect of agonal-pH state. Genes with the least sensitivity to agonal-pH could present a starting point for candidate gene search in neuropsychiatric disorders. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe pathophysiology of depression and mania is largely unknown leaving open a question of which cellular pathway(s) to investigate. Gene expression screening is a powerful method for probing alterations in neural functions in mood disorder. Examining gene expression profiles has been extremely useful for establishing different phenotypes in cancer. [1][2][3] Various microarray profiles in mood disorder have been reported that use different microarray platforms, analysis methodology, regional differences, agonal factors and brain pH. [4][5][6][7][8][9][10][11][12][13][14] Presumably, a substantial heterogeneity in the pathophysiology of mood disorder coupled with small sample sizes and small fold changes contributes to the lack of consistency among the findings. 15 In five microarray studies a broad mitochondrial dysfunction was reported in neuropsychiatric disorders. 10,11,14,[16][17][18] One study of bipolar disorder (BPD) focused on a broad set of mitochondrial-related gene expression and found that in general, mitochondrial gene expression was predominantly decreased in BPD compared to controls in the dorsolateral pre-frontal cortex (DLPFC) when using Stanley samples...

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“…The deregulation of several proteins like RB (Ledl et al, 2005), SENP1 (Veltman et al, 2005), PIAS3 (Wang and Banerjee 2004), PIASy (Ueda et al, 2003), SUMO1 (Villalva et al, 2002), SUMO2 (Lee 2004) etc. by SUMOylation and its involvement in cancers of different kinds provides an opportunity to exploit SUMOylation as anticancer drug target.…”

Section: Sumoylation and Anticancer Drugsmentioning

confidence: 99%

SUMOylation: A link to future therapeutics

2016

Current Issues in Molecular Biology

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SUMOylation, much of a similar process like ubiquitination catches attention across various research groups as a potential therapeutic target to fight various infectious and cancerous diseases. This idea take its strength from recent reports which unearth the molecular mechanisms of SUMOylation and its involvement in important diseases distributed across various kingdoms. At the beginning SUMOylation was considered a process affected only by viral diseases but subsequent reports enlighten its role in diseases caused by bacteria as well. This enhances the SUMOylation canvas and demanded more in-depth study of the process. The present review is an attempt to study the regulatory mechanism of genes when the natural SUMOylation pathway is disturbed, the cross-talk among SUMOylation and other post translational modifications, the role of miRNAs in controlling the function of transcripts, loading of RNA species into exosomes and the possible SUMOylation related therapeutic targets. IntroductionThe innate immune responses across kingdoms are tightly regulated to fight attacking pathogens. Post translational modification of proteins like acetylation, methylation, ubiquitination and SUMOylation have predominant role in activation/deactivation of immune responses by regulating various cellular processes including transcription, DNA repair, proliferation and apoptosis as these have the potential to relocate the protein to different organelles and modify its biological function. The deep understanding of those post translational mechanisms could provide insights in controlling several disease conditions and develop therapeutics based on those post translational modification markers.The small ubiquitin like modifiers (SUMO) proteins discovered in 1997 (Mahajan et al., 1997) has since been recognized as family of important modification proteins unlike ubiquitination which is involved in degradation of proteins, instead it modulates the function of target proteins. The covalent conjugation of SUMO molecules to protein residue lysine on a typical consensus sequence ψKxD/E (where ψ is large hydrophobic residue, K is the target lysine, D/E is acidic residue and x represent any amino acid) (Rodriguez et al., 2001;Sampson et al., 2001). The process of SUMOylation is carried out by a cascade of three enzymes (E1, E2 and E3). E1 is a SUMO activating enzyme SAE1, while E2 is conjugating enzyme e.g. Ubc9 and E3 is SUMO ligase. The SUMOylation reaction is reversed by SENPs termed as deSUMOylation having distinct regulatory roles. Till date four SUMO molecules have been reported in mammals viz., SUMO1, SUMO2, SUMO3 and SUMO4. The sequence similarity of SUMO2 and SUMO3 are almost 97% hence are often reported collectively as SUMO2/3. Various kinds of stimuli like oxidative stress often increase the rate of SUMOylation. A recent report shows the exposure to cigarette smoke alters the microRNA expression by SUMOylation of DICER (Gross et al., 2014). Viruses and chemical toxins also causes an increase in SUMOylation, a well known exam...

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DNA microarray analysis of stage progression mechanism in myelodysplastic syndrome

Cited by 61 publications

References 25 publications

Epigenetic regulation of signal transducer and activator of transcription 3 in acute myeloid leukemia

Epigenetic regulation of signal transducer and activator of transcription 3 in acute myeloid leukemia

Mitochondrial-related gene expression changes are sensitive to agonal-pH state: implications for brain disorders

SUMOylation: A link to future therapeutics

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