Epigenetic changes: a common theme in acute myelogenous leukemogenesis

Gutiérrez, Soraya E.; Romero-Oliva, Francisco A

doi:10.1186/1756-8722-6-57

Cited by 41 publications

(43 citation statements)

References 110 publications

(106 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among the major fusion partners of MLL are the transcriptional activators AF4, AF9, AF10, and ENL [57]. These fusion proteins usually lead to the overexpression of MLL target genes, including HOXA9 and MEIS1, which are required for hematopoietic stem cell (HSC) self-renewal [58][59][60]. Studies on mouse models have shown a crucial role for MLL in the control of HOX gene expression [54].…”

Section: Mll Fusion Proteinsmentioning

confidence: 99%

Epigenetic alterations in acute myeloid leukemias

2014

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is a heterogeneous disease for which the standard treatment with cytotoxic chemotherapy has remained largely unchanged for over four decades, with unfavorable clinical results. Epigenetic alterations have been described in several AMLs, and in some cases their origin has been studied in detail mechanistically (such as in acute promyelocytic leukemia, caused by the promyelocytic leukemia-retinoic acid receptor-a fusion protein). Recently, the advent of massive parallel sequencing has revealed that > 70% of AML cases have mutations in DNA methylation-related genes or mutations in histone modifiers, showing that epigenetic alterations are key players in the development of most, if not all, AMLs, and pointing to the exploitation of new molecular targets for more efficacious therapies. This review provides a brief overview of the latest findings on the characterization of the epigenetic landscape of AML and discusses the rationale for the optimization of epigenetic therapy of AML.

show abstract

Section: Mll Fusion Proteinsmentioning

confidence: 99%

Epigenetic alterations in acute myeloid leukemias

2014

View full text Add to dashboard Cite

show abstract

“…A growing number of genetic (11)(12)15), epigenetic (16), and regulatory aberrations (17)(18) relevant for leukemogenesis and risk stratification has been described. Despite this knowledge, the impact of these factors on clinical course and on cell properties is not well-defined (12,19,20).…”

Section: Introductionmentioning

confidence: 99%

Cell Division Patterns in Acute Myeloid Leukemia Stem-like Cells Determine Clinical Course: A Model to Predict Patient Survival

et al. 2015

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is a heterogeneous disease in which a variety of distinct genetic alterations might occur. Recent attempts to identify the leukemia stem-like cells (LSC) have also indicated heterogeneity of these cells. On the basis of mathematical modeling and computer simulations, we have provided evidence that proliferation and self-renewal rates of the LSC population have greater impact on the course of disease than proliferation and self-renewal rates of leukemia blast populations, that is, leukemia progenitor cells. The modeling approach has enabled us to estimate the LSC properties of 31 individuals with relapsed AML and to link them to patient survival. On the basis of the estimated LSC properties, the patients can be divided into two prognostic groups that differ significantly with respect to overall survival after first relapse. The results suggest that high LSC self-renewal and proliferation rates are indicators of poor prognosis. Nevertheless, high LSC self-renewal rate may partially compensate for slow LSC proliferation and vice versa. Thus, model-based interpretation of clinical data allows estimation of prognostic factors that cannot be measured directly. This may have clinical implications for designing treatment strategies. Cancer Res; 75(6); 940-9. Ó2015 AACR.

show abstract

“…Enzymes that catalyze post-transcriptional modification of histones such as histone acetylation and methylation are frequently dysregulated in AML (96,97). The most commonly dysregulated histone modifier in AML, the Mixed Lineage Leukemia protein (MLL), is a histone methyltransferase that is involved in gene fusions and partial tandem duplications (MLL-PTD) (98).…”

Section: Histone Aberrationsmentioning

confidence: 99%