Role of Epigenetics in Chronic Myeloid Leukemia

Poláková, Kateřina Machová; Koblihova, Jitka; Stopka, Tomáš

doi:10.1007/s11899-012-0152-z

Cited by 49 publications

(35 citation statements)

References 58 publications

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“…BCR promoter methylation correlates with a better response to IM through events likely encompassing BCR‐ABL1 transcription [Koh et al, ]. Moreover, BCR‐ABL1 ‐associated DNA hyper‐methylation affects genes coding for transcription factors (JunB, IRF‐4, CEBPA, HOXA4, PU.1, TFAP2A, and EBF1), tumor suppressors (SOCS1, PLCD1, DAPK1, PTPRG, and DDIT3), and tumor‐associated antigens (PRAME) [Machova et al, ; Leo and Martinelli, ]. The identification of DNMT1 as a component of DNA hyper‐methylation leading to transcriptional down‐modulation of C22 orf 2 and BCL2‐like11 tumor suppressor genes involved in BCR‐ABL1 leukemogenesis support the use of DNMT1‐targeting agents in treatment of advanced phases or resistant to IM CML [Katarjian et al, ; Issa et al, ; Oki et al, ].…”

Section: Discussionmentioning

confidence: 99%

DNA Methyltransferase 1 Drives Transcriptional Down‐Modulation of β Catenin Antagonist Chibby1 Associated With the BCR‐ABL1 Gene of Chronic Myeloid Leukemia

Leo

Mancini

Castagnetti

et al. 2015

J of Cellular Biochemistry

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The decrease of Chibby1 (CBY1) contributes to β catenin constitutive activation associated with the presence of the BCR-ABL1 fusion gene of chronic myeloid leukemia (CML). This is mediated by transcriptional events and driven by DNA hyper-methylation at promoter-associated CpG islands of the CBY1-encoding gene C22orf2. Moreover, CBY1 transcriptional induction proceeding from promoter de-methylation is a component of BCR-ABL1+ cell response to Imatinib (IM). Our study showed that DNA methyltransferase 1 (DNMT1) has a central role in the hyper-methylation at the C22orf2 promoter. Further investigation in leukemic hematopoietic progenitors from IM-responsive and IM-resistant CML patients at diagnosis failed to demonstrate any correlation between DNMT1-driven hyper-methylation of the C22orf2 promoter and response to IM. Notably, the response to IM was neither predicted by DNMT1-driven hyper-methylation of BCL2-like11 at diagnosis. In conclusion, the hypermethylation of C22orf2 and BCL2-like11 promoters proceeding from DNMT1 is a crucial component of their reduced expression, but it is not directly involved in CML resistance to IM. It might rather contribute to the disease evolution towards a drug-resistant phenotype in more advanced phases or blast crisis.

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Section: Discussionmentioning

confidence: 99%

DNA Methyltransferase 1 Drives Transcriptional Down‐Modulation of β Catenin Antagonist Chibby1 Associated With the BCR‐ABL1 Gene of Chronic Myeloid Leukemia

Leo

Mancini

Castagnetti

et al. 2015

J of Cellular Biochemistry

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“…BC is the result of maintained BCR-ABL activity, leading to genetic instability, DNA damage, and impaired DNA repair [56]. Machova Polakova, K et al reported decreased levels of four miRNAs, including miR-144 in PB cells from blast crisis [57].…”

Section: Mir-144 In Chronic Myeloid Leukemiamentioning

confidence: 99%

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

Kooshkaki

Rezaei

Rahmati

et al. 2020

IJMS

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MicroRNAs (miRNAs) are small and non-coding RNAs that display aberrant expression in the tissue and plasma of cancer patients when tested in comparison to healthy individuals. In past decades, research data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been confirmed that miRNAs can act either as oncogenes by silencing tumor inhibitors or as tumor suppressors by targeting oncoproteins. MiR-144s are located in the chromosomal region 17q11.2, which is subject to significant damage in many types of cancers. In this review, we assess the involvement of miR-144s in several cancer types by illustrating the possible target genes that are related to each cancer, and we also briefly describe the clinical applications of miR-144s as a diagnostic and prognostic tool in cancers.Int. J. Mol. Sci. 2020, 21, 2578 2 of 23 of a mRNA molecule [3]. MiRNAs indicate a new perspective in the study of cancers. More than 50% of miRNA genes were discovered to be located within the genomic regions that are involved in cancers, suggesting their role in human cancer pathogenesis. In pathological conditions, MiRNAs can negatively regulate gene expression and they are associated with tumor growth, apoptosis, invasion, and metastasis. In the past, several studies have indicated the ability of miRNAs in the inhibition of tumors as a critical option for the improvement of cancer therapy [4,5]. Tumor activator miRNAs, called oncomiRs, are overexpressed in various cancers. On the contrary, suppressive tumor miRNAs are underexpressed [6][7][8]. Among several miRNAs assessed, miR-144s seem to have a role in several cancers. These miRNAs are located in the chromosomal region 17q11.2, being significantly destroyed in many types of cancers. The predicted stem-loop structure of miR-144s recognized by the miRBase (http://mirbase.org/) is shown in Figure 1A. The miR-144 hairpin gives rise to the "guide strand" miR-144-5p and the sister "passenger" strand miR-144-3p ( Figure 1B).

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“…This scenario now looks to be achievable with growing evidence that CML stem cells use survival signals other than BCR‐ABL kinase to maintain their viability in the presence of TKI. Also, although BCR‐ABL may be the initiating oncogene in CML, additional genetic and/or epigenetic events (including aberrant methylation of ABL1, p15, ATG16L2, and DAPk1) could be responsible for maintaining the disease independently of, or in addition to, the initial transformation caused by the chromosomal translocation . As with many other forms of cancer, CML development and progression does not result from the activity of a single driver but may require tightly regulated cooperation of several mutations at the genetic level .…”

Section: Resultsmentioning

confidence: 99%

Concise Review: Cancer Cells Escape from Oncogene Addiction: Understanding the Mechanisms Behind Treatment Failure for More Effective Targeting

2014

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Oncogene addiction describes the dependence of some cancers on one or a few genes for their survival. Inhibition of the corresponding oncoproteins can lead to dramatic responses. However, in some cases, such as chronic myeloid leukemia (CML), a disease characterized by the presence of the abnormal fusion tyrosine kinase BCR‐ABL, cancer stem cells may never acquire addiction to the oncogene that drives disease development. The suggested mechanism(s) for treatment failure include a quiescent stem cell population capable of reinstating disease, high levels of oncoprotein expression, or acquired mutations in the oncogene. In this review, we discuss the evidence for oncogene addiction in several solid tumors and their potential escape mechanism(s) with a particular focus on CML stem cells. Stem Cells 2014;32:1373–1379

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Role of Epigenetics in Chronic Myeloid Leukemia

Cited by 49 publications

References 58 publications

DNA Methyltransferase 1 Drives Transcriptional Down‐Modulation of β Catenin Antagonist Chibby1 Associated With the BCR‐ABL1 Gene of Chronic Myeloid Leukemia

DNA Methyltransferase 1 Drives Transcriptional Down‐Modulation of β Catenin Antagonist Chibby1 Associated With the BCR‐ABL1 Gene of Chronic Myeloid Leukemia

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

Concise Review: Cancer Cells Escape from Oncogene Addiction: Understanding the Mechanisms Behind Treatment Failure for More Effective Targeting

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