MYBL2 (B-Myb): a central regulator of cell proliferation, cell survival and differentiation involved in tumorigenesis

Musa, Julian; Aynaud, Marie-Ming; Mirabeau, Olivier; Delattre, Olivier; Grünewald, Thomas G.P.

doi:10.1038/cddis.2017.244

Cited by 245 publications

(215 citation statements)

References 118 publications

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“…Consistent with the enrichment of DEGs for cell cycle genes, E2F and MYB consensus-binding motifs were identified as the top two motifs enriched amongst genes downregulated in IsoHD-81Q organoids ( Figure 4D). The transcription factors (TF) E2F and MYB play a key role in cell cycle control [38,39]. Expression levels of several members of the E2F TF family such as E2F1, E2F3, E2F4 and E2F5 were significantly lower in IsoHD-81Q compared with 30Q organoids ( Figure 4E).…”

Section: Rna-seq Analysis Reveals Disruption Of Key Cell Cycle Regulamentioning

confidence: 99%

Expanded huntingtin CAG repeats disrupt the balance between neural progenitor expansion and differentiation in human cerebral organoids

Zhang

Ooi

Utami

et al. 2019

Preprint

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Huntington disease (HD) manifests in both adult and juvenile forms. Mutant HTT gene carriers are thought to undergo normal brain development followed by a degenerative phase, resulting in progressive clinical manifestations. However, recent studies in children and prodromal individuals at risk for HD have raised the possibility of abnormal neurodevelopment.Although key findings in rodent models support this notion, direct evidence in the context of human physiology remains lacking. Using a panel of isogenic HD human embryonic pluripotent stem cells and cerebral organoids, we investigated the impact of mutant HTT on early neurodevelopment. We find that ventricular zone-like neuroepithelial progenitor layer expansion is blunted in an HTT CAG repeat length-dependent manner due to premature neurogenesis in HD cerebral organoids, driven by cell intrinsic processes. Transcriptional profiling and imaging analysis revealed impaired cell cycle regulatory processes, increased G1 length, and increased asymmetric division of apical progenitors, collectively contributing to premature neuronal differentiation. We demonstrate increased activity of the ATM-p53 pathway, an up-stream regulator of cell cycle processes, and show that treatment with ATM antagonists partially rescues the blunted neuroepithelial progenitor expansion in HD organoids. Our findings suggest that CAG repeat length regulates the balance between neural progenitor expansion and differentiation during early neurodevelopment. Our results 1/26further support the view that HD, at least in its early-onset forms, may not be a purely neurodegenerative disorder, and that abnormal neurodevelopment may be a component of HD pathophysiology.

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Section: Rna-seq Analysis Reveals Disruption Of Key Cell Cycle Regulamentioning

confidence: 99%

Expanded huntingtin CAG repeats disrupt the balance between neural progenitor expansion and differentiation in human cerebral organoids

Zhang

Ooi

Utami

et al. 2019

Preprint

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“…In addition, mutations in IDH1 is reported to be highly correlated with higher expression of ZIP11, suggesting a possible synergistic interaction between IDH1 and ZIP11 [47]. MYBL2 (rs285206) has an essential role in cell cycle progression, cell survival, and cell differentiation, and is found to be overexpressed in multiple cancer cases [48]. Overexpression of MYBL2 is suggested to have a prognostic value for disease-free survival and cumulative incidence of remission for AML patients [48,49].…”

Section: Discussionmentioning

confidence: 99%

Iterative feature selection method to discover predictive variables and interactions for high-dimensional transplant genomic data

Huang

Vierra-Green²,

Spellman³

et al. 2019

Preprint

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After allogeneic hematopoietic stem cell transplantation (allo-HCT), donor-derived immune cells can trigger devastating graft-versus-host disease (GVHD). The clinical effects of GVHD are well established; however, genetic mechanisms that contribute to the condition remain unclear.Candidate gene studies and genome-wide association studies have shown promising results, but they are limited to a few functionally derived genes and those with strong main effects. Transplantrelated genomic studies examine two individuals simultaneously as a single case, which adds additional analytical challenges. In this study, we propose a hybrid feature selection algorithm, iterative Relief-based algorithm followed by a random forest (iRBA-RF), to reduce the SNPs from the original donor-recipient paired genotype data and select the most predictive SNP sets in association with the phenotypic outcome in question. The proposed method does not assume any main effect of the SNPs; instead, it takes into account the SNP interactions. We applied the iRBA-RF to a cohort (n=331) of acute myeloid leukemia (AML) patients and their fully 10 of 10 (HLA-A, -B, -C, -DRB1, and -DQB1) HLA-matched healthy unrelated donors and assessed two casecontrol scenarios: AML patients vs healthy donor as case vs control and acute GVHD group vs non-GVHD group as case vs control, respectively. The results show that iRBA-RF can efficiently reduce the size of SNPs set down to less than 0.05%. Moreover, the literature review showed that the selected SNPs appear functionally involved in the pathologic pathways of the phenotypic diseases in question, which may potentially explain the underlying mechanisms. This proposed method can effectively and efficiently analyze ultra-high dimensional genomic data and could help provide new insights into the development of transplant-related complications from a genomic perspective.

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“…MAX could also be either an enhancer (forming heterodimers with MYC, MYC-MAX) or a repressor (forming heterodimers with MAD, MAD-MAX or homodimers, MAX-MAX) (34–36). Overexpression of MYBL2 has been found in several cancer types and associated with poor patient outcomes (review in (37)). Moreover, studies in cell lines suggest that overexpression of MYBL2 is associated with resistance to chemotherapeutic agents (including etoposide) and radiation (38–40).…”

Section: Discussionmentioning

confidence: 99%

Common TDP1 Polymorphisms in Relation to Survival among Small Cell Lung Cancer Patients: A Multicenter Study from the International Lung Cancer Consortium

Lohavanichbutr

Sakoda

Amos

et al. 2017

Clinical Cancer Research

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Background DNA topoisomerase inhibitors are commonly used for treating small cell lung cancer (SCLC). Tyrosyl-DNA phosphodiesterase (TDP1) repairs DNA damage caused by this class of drugs and may therefore influence treatment outcome. In this study, we investigated whether common TDP1 single nucleotide polymorphisms (SNPs) are associated with overall survival among SCLC patients. Methods Two TDP1 SNPs (rs942190 and rs2401863) were analyzed in 890 patients from 10 studies in the International Lung Cancer Consortium (ILCCO). The Kaplan-Meier method and Cox regression analyses were used to evaluate genotype associations with overall mortality at 36 months post-diagnosis, adjusting for age, sex, race, and tumor stage. Results Patients homozygous for the minor allele (GG) of rs942190 had poorer survival compared to those carrying AA alleles, with a hazard ratio (HR) of 1.36 (95% confidence interval (CI): 1.08–1.72, p-value=0.01), but no association with survival was observed for patients carrying the AG genotype (HR=1.04, 95% CI:0.84–1.29, p-value=0.72). For rs2401863, patients homozygous for the minor allele (CC) tended to have better survival than patients carrying AA alleles (HR=0.79, 95% CI: 0.61–1.02, p-value=0.07). Results from the Genotype Tissue Expression (GTEx) Project, the Encyclopedia of DNA Elements (ENCODE), and the ePOSSUM web application support the potential function of rs942190. Conclusions We found the rs942190 GG genotype to be associated with relatively poor survival among SCLC patients. Further investigation is needed to confirm the result and to determine whether this genotype may be a predictive marker for treatment efficacy of DNA topoisomerase inhibitors.

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MYBL2 (B-Myb): a central regulator of cell proliferation, cell survival and differentiation involved in tumorigenesis

Cited by 245 publications

References 118 publications

Expanded huntingtin CAG repeats disrupt the balance between neural progenitor expansion and differentiation in human cerebral organoids

Expanded huntingtin CAG repeats disrupt the balance between neural progenitor expansion and differentiation in human cerebral organoids

Iterative feature selection method to discover predictive variables and interactions for high-dimensional transplant genomic data

Common TDP1 Polymorphisms in Relation to Survival among Small Cell Lung Cancer Patients: A Multicenter Study from the International Lung Cancer Consortium

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