Epigenetic diversity in hematopoietic neoplasms

Shaknovich, Rita; De, Subhajyoti; Michor, Franziska

doi:10.1016/j.bbcan.2014.09.003

Cited by 13 publications

(15 citation statements)

References 122 publications

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“…That is why cancer therapies now aim at the induction of important silenced genes implicated in cell metabolism by the deactivation of DNMTs or the inhibition of histone deacetylation. This is particularly important in the treatment of hematologic malignancies, where the balance between the hematopoietic stem cell self-renewal and the activation of differentiation processes is modulated by epigenetic mechanisms [3][4][5]. Demethylating drugs specifically target the complex landscape of molecular alterations characterizing the hematologic malignancies to restore a normal hematopoietic differentiation [6,7].…”

Section: Introductionmentioning

confidence: 99%

An increased expression of PI-PLCβ1 is associated with myeloid differentiation and a longer response to azacitidine in myelodysplastic syndromes

Cocco

Finelli

Mongiorgi

et al. 2015

Journal of Leukocyte Biology

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This study tested the hypothesis that PI-PLCβ1 is associated with myeloid differentiation and that its expression could be useful for predicting the response of MDS patients to azacitidine, as the clinical effect of epigenetic treatments is often detectable only after several cycles of therapy. To this end, PI-PLCβ1 was quantified on 70 MDS patients (IPSS risk: 13 Low, 20 Int-1, 31 Int-2, 6 High) at baseline and during the first 3 cycles of azacitidine. Results were then compared with the hematologic response, as assessed after the sixth cycle of azacitidine therapy. Overall, 60 patients completed 6 cycles of azacitidine, and for them, a clinical and molecular evaluation was possible: 37 of these patients (62%) showed a specific increase of PI-PLCβ1 mRNA within the first 3 cycles, which was associated with a longer duration of response and with an increased myeloid differentiation, as evidenced by PI-PLCγ2 induction and the recruitment of specific myeloid-associated transcription factors to the PI-PLCβ1 promoter during azacitidine response. Moreover, the increase of cyclin D3 gene expression throughout all of the therapy showed that PI-PLCβ1-dependent signaling is indeed activated in azacitidine responder patients. Taken together, our results show that PI-PLCβ1 quantification in MDS predicts the response to azacitidine and is associated with an increased myeloid differentiation.

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Section: Introductionmentioning

confidence: 99%

An increased expression of PI-PLCβ1 is associated with myeloid differentiation and a longer response to azacitidine in myelodysplastic syndromes

Cocco

Finelli

Mongiorgi

et al. 2015

Journal of Leukocyte Biology

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“…78 Altered epigenetic marks of different genes are described in several cancers regardless of anatomic region. 79,80 Some of them are considered as possible diagnostic and prognostic cancer markers. 81 DNA methylation is especially interesting because of its stability and simple accessibility in routine molecular diagnostic laboratories.…”

Section: Epigenetic Mechanisms and Circadian Clockmentioning

confidence: 99%

Circadian rhythms and new options for novel anticancer therapies

Zmrzljak¹

2015

CPT

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The patterns of activity/sleep, eating/fasting, etc show that our lives are under the control of an internal clock. Cancer is a systemic disease that affects sleep, feeding, and metabolism. All these processes are regulated by the circadian clock on the one hand, but on the other hand, they can serve as signals to tighten up the patient's circadian clock by robust daily routine. Usually, anticancer treatments take place in hospitals, where the patient's daily rest/activity pattern is changed. However, it has been shown that oncology patients with a disturbed circadian clock have poorer survival outcomes. The administration of different anticancer therapies can disturb the circadian cycle, but many cases show that circadian rhythms in tumors are deregulated per se. This fact can be used to plan anticancer therapies in such a manner that they will be most effective in antitumor action, but least toxic for the surrounding healthy tissue. Metabolic processes are highly regulated to prevent waste of energy and to ensure sufficient detoxification; as a consequence, xenobiotic metabolism is under tight circadian control. This gives the rationale for planning the administration of anticancer therapies in a chronomodulated manner. We review some of the potentially useful clinical praxes of anticancer therapies and discuss different possible approaches to be used in drug development and design in the future.

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“…In line with the Waddington concept, it has been shown that the potential of somatic cells to be reprogrammed into induced pluripotent stem (iPS) cells can be increased by disturbing their epigenetic state with treatments affecting histone modifications and creating epigenetic heterogeneity before factor induction (Pour et al 2015). Cancer is another pivotal example of epigenetic heterogeneity, a factor that contributes to tumour cell plasticity, and might therefore be the major underlying cause for poor prognosis and survival rates for several cancers, including prostate cancer , Brocks et al 2014, Shaknovich et al 2014.…”

Section: Epigenetic Heterogeneitymentioning

confidence: 99%

On the origin of sperm epigenetic heterogeneity

2016

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The influence of epigenetic modifications on reproduction and on the function of male germ cells has been thoroughly demonstrated. In particular, aberrant DNA methylation levels in sperm have been associated with abnormal sperm parameters, lower fertilization rates and impaired embryo development. Recent reports have indicated that human sperm might be epigenetically heterogeneous and that abnormal DNA methylation levels found in the sperm of infertile men could be due to the presence of sperm populations with different epigenetic quality. However, the origin and the contribution of different germ cell types to this suspected heterogeneity remain unclear. In this review, we focus on sperm epigenetics at the DNA methylation level and its importance in reproduction. We take into account the latest developments and hypotheses concerning the functional significance of epigenetic heterogeneity coming from the field of stem cell and cancer biology and discuss the potential importance and consequences of sperm epigenetic heterogeneity for reproduction, male (in)fertility and assisted reproductive technologies (ART). Based on the current information, we propose a model in which spermatogonial stem cell variability, either intrinsic or due to external factors (such as endocrine action and environmental stimuli), can lead to epigenetic sperm heterogeneity, sperm epimutations and male infertility. The elucidation of the precise causes for epimutations, the conception of adequate therapeutic options and the development of sperm selection technologies based on epigenetic quality should be regarded as crucial to the improvement of ART outcome in the near future.Reproduction (2016) 151 R71-R78

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Epigenetic diversity in hematopoietic neoplasms

Cited by 13 publications

References 122 publications

An increased expression of PI-PLCβ1 is associated with myeloid differentiation and a longer response to azacitidine in myelodysplastic syndromes

An increased expression of PI-PLCβ1 is associated with myeloid differentiation and a longer response to azacitidine in myelodysplastic syndromes

Circadian rhythms and new options for novel anticancer therapies

On the origin of sperm epigenetic heterogeneity

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