Transcription analysis of a histones modifiers panel coupled with critical tumor suppressor genes displayed frequent changes in patients with AML.

Amiri, Vahid; Mohammadi, Mohammad Hossein; Rafiee, Mohammad; Ghezelbash, Behrooz; Salari, Sina; Farsani, Mehdi Allahbakhshian

doi:10.1016/j.retram.2021.103311

Cited by 3 publications

(5 citation statements)

References 42 publications

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“…However, to our knowledge, the current study showed for the first time that EHMT2/G9a and KDM2b were highly expressed in adult and pediatric de novo AML patients and investigated their relation to patients' clinical features and survival status. Recently, one research showed that KDM2b expression level was not significantly changed between AML patients and control cases 29 . Perhaps different results between the present study and that paper are due to the sample size variation, in our study of 110 versus 50 patients.…”

Section: Discussioncontrasting

confidence: 79%

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Expression and prognostic significance of chromatin modulators EHMT2/G9a and KDM2b in acute myeloid leukemia

Gouda

Zidane

Abdelhady

et al. 2022

J of Cellular Biochemistry

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Epigenetics factors are critical for normal cell function and their regulation is sensitive to malignancy development. EHMT2/G9a and KDM2b are key epigenetics players in different cancer types. However, their expression profiles and related consequences in acute myeloid leukemia (AML) patients have not been known yet. In addition to routine lab work, expression levels of EHMT2/G9a and KDM2b were determined in 110 adult and pediatric patients with De Novo AML. Relations between their expression and patients' clinical data were tested by statistical methods. EHMT2/G9a and KDM2b were highly expressed in AML patients against control cases and associated with the presence of adverse genomic alterations. In response to induction chemotherapy, EHMT2/G9a and KDM2b showed to be significantly high in resistant and relapsed patients in comparison to the complete remission group. KDM2b overexpression was associated with CD11c (integrin alpha X) downregulation. Kaplan−Meier analysis indicated that EHMT2/G9a and KDM2b overexpression was correlated with poor survival status in AML patients. We conclude that EHMT2/G9a and KDM2b expression levels could be used as independent prognostic factors for AML disease.

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Section: Discussioncontrasting

confidence: 79%

“…Recently, one research showed that KDM2b expression level was not significantly changed between AML patients and control cases. 29 Perhaps different results between the present study and that paper are due to the sample size variation, in our study of 110 versus 50 patients.…”

Section: Discussioncontrasting

confidence: 78%

Expression and prognostic significance of chromatin modulators EHMT2/G9a and KDM2b in acute myeloid leukemia

Gouda

Zidane

Abdelhady

et al. 2022

J of Cellular Biochemistry

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“…Expressions of UHRF2 are reduced in many types of human cancers, including acute myeloid leukemia, gastric cancer, pancreatic cancer, lung cancer, and head and neck cancer [ 1 , 2 , 5 , 9 ]. Loss of UHRF2 is associated with progression of cancer [ 6 , 8 ] and UHRF2 is a negative regulator of epithelial–mesenchymal transition [ 7 ], suggesting the role of UHRF2 as a tumor suppressor.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding hematologic cancers, UHRF2 is barely expressed in some leukemic cell lines, including K562, Jurkat, and RAJI cells, while it is significantly expressed in RS4:11, SEMK, and NALM6 cells [ 5 ]. However, primary cells from most acute myeloid leukemia patients showed low UHRF2 mRNA levels [ 5 , 9 ]. On the other hand, it has been reported that Uhrf2 deletion reduced progression of colon cancer with low Apc expression in mice [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Impaired Repopulating Ability of Uhrf2−/− Hematopoietic Progenitor Cells in Mice

Sano

Ueda

Minakawa

et al. 2023

Genes

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UHRF proteins catalyze the ubiquitination of target proteins and are involved in regulating gene expression. Some studies reported a reduced expression of UHRF2 in acute leukemia cells, but the role of UHRF2 in hematopoiesis remains unknown. Here, we generated Uhrf2−/− mice to clarify the role of UHRF2 deletion in hematopoiesis. Compared to Uhrf2+/+ mice, Uhrf2−/− mice showed no differences in complete blood counts, as well as bone marrow (BM) findings and spleen weights. Proportions of cells in progenitor fractions in BM were comparable between Uhrf2+/+ mice and Uhrf2−/− mice. However, in competitive repopulation assays with BM transplants (BMT), the proportions of Uhrf2−/− cells were decreased relative to Uhrf2+/+ cells in all lineages. After the second BMT, Uhrf2−/− neutrophils were few, while 20–30% of Uhrf2−/− T cells and B cells were still detected. RNA sequencing showed downregulation of some genes associated with stem-cell function in Uhrf2−/− hematopoietic stem/progenitor cells (HSPCs). Interestingly, trimethylated histone H3 lysine 9 was increased in Uhrf2−/− HSPCs in a cleavage under targets and tagmentation assay. While UHRF2 deletion did not cause hematologic malignancy or confer a growth advantage of HSPCs, our results suggest that UHRF2 may play a role in the regulation of hematopoiesis.

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“…The effects of different environmental factors could be recorded in cellular memory through epigenetic changes (11,12). In cancers, regardless of whether the alterations are genetically or epigenetically, they exert pleiotropic effects on gene expression.…”

Section: Introductionmentioning

confidence: 99%

Panobinostat, a Pan-HDAC Inhibitor, Substantially Decreases the Quiescent Population of Leukemic Cells either in Monoculture or in Co-culture with Bone Marrow Stromal Cells.

et al. 2022

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Background: It is increasingly evident that interactions between leukemic cells and their niches can have profound effects on clinical outcomes and have been contributed to the failure in treatment and drug shortage in the eradication of minimal residual disease, at least in part, through moving the cells from proliferative state to quiescent state. Objectives: We, therefore, investigated the effects of different bone marrow stromal cells (BMSCs) on the induction of quiescence and tested the advantage of pan-HDAC inhibitor panobinostat in the induction of apoptosis and targeting the quiescence cells of APL-derived (NB4) and CML-derived (K562) cell lines. Methods: We firstly evaluated the effect of BMSCs including mesenchymal stem cell (MSC), osteoblast, and macrophage on the induction of NB4 and K562 cells quiescence in co-culture models. Next, the alterations in mRNA expression of quiescence-related genes and leukemia-driver oncogenes were evaluated in different models. Finally, the anti-leukemic effects of panobinostat were evaluated, using MTT assay and evaluation of apoptosis and G0 population. Results: Upon 10 days of co-culture with stromal cells, we found that leukemic cells significantly accumulated in the G0 phase. The co-cultured cells also depictured an overall overexpression of most quiescence promoter genes. The oncogenes were underexpressed in the majority of co-cultured models. The results also showed that although panobinostat could induce apoptosis in co-cultured cells, its effect on the reduction of the G0 population was more striking. Conclusions: These data propose that leukemia cells' quiescence state induced by stromal cells is reversible by HDAC inhibition and panobinostat could be a potentiate drug for eradication of treatment-resistance quiescence leukemic cells.

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Transcription analysis of a histones modifiers panel coupled with critical tumor suppressor genes displayed frequent changes in patients with AML.

Cited by 3 publications

References 42 publications

Expression and prognostic significance of chromatin modulators EHMT2/G9a and KDM2b in acute myeloid leukemia

Expression and prognostic significance of chromatin modulators EHMT2/G9a and KDM2b in acute myeloid leukemia

Impaired Repopulating Ability of Uhrf2−/− Hematopoietic Progenitor Cells in Mice

Panobinostat, a Pan-HDAC Inhibitor, Substantially Decreases the Quiescent Population of Leukemic Cells either in Monoculture or in Co-culture with Bone Marrow Stromal Cells.

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