ArticleJournal of hematology & oncology2014
Homeobox gene expression in acute myeloid leukemia is linked to typical underlying molecular aberrations.
Article in Journal of hematology & oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 20 citations in OpenAlex.
- Transcriptome-based molecular subgroup identification and prognosis stratification in pediatric AML.Annals of hematology · 2025Article
- Identification of HOXA9 methylation as an epigenetic biomarker predicting prognosis and guiding treatment choice in acute myeloid leukemia.BMC cancer · 2025Article
- Overexpression of HOXA10 is associated with unfavorable prognosis of acute myeloid leukemia.BMC cancer · 2020Article
- DNA Methylation of Enhancer Elements in Myeloid Neoplasms: Think Outside the Promoters?Cancers · 2019Review
- Low HOX gene expression in PML-RARα-positive leukemia results from suppressed histone demethylation.Epigenetics · 2018Article
- DNA methylation profiling reveals common signatures of tumorigenesis and defines epigenetic prognostic subtypes of canine Diffuse Large B-cell Lymphoma.Scientific reports · 2017Article
- PML-RAR alpha induces the downmodulation of HHEX: a key event responsible for the induction of an angiogenetic response.Journal of hematology & oncology · 2016Article
- Molecular alterations in the TCR signaling pathway in patients with aplastic anemia.Journal of hematology & oncology · 2016Article
- GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways.Journal of hematology & oncology · 2016Article
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough distinct patterns of homeobox (HOX) gene expression have been described in defined cytogenetic and molecular subsets of patients with acute myeloid leukemia (AML), it is unknown whether these patterns are the direct result of transcriptional alterations or rather represent the differentiation stage of the leukemic cell.
methodTo address this question, we used qPCR to analyze mRNA expression of HOXA and HOXB genes in bone marrow (BM) samples of 46 patients with AML and sorted subpopulations of healthy BM cells. These various stages of myeloid differentiation represent matched counterparts of morphological subgroups of AML. To further study the transcriptional alterations of HOX genes in hematopoiesis, we also analyzed gene expression of epigenetic modifiers in the subpopluations of healthy BM and leukemic cells.
resultsUnsupervised hierarchical clustering divided the AMLs into five clusters characterized by the presence of prevalent molecular genetic aberrations. Notably, the impact of genotype on HOX gene expression was significantly more pronounced than that of the differentiation stage of the blasts. This driving role of molecular aberrations was best exemplified by the repressive effect of the PML-RARa fusion gene on HOX gene expression, regardless of the presence of the FLT3/ITD mutation. Furthermore, HOX gene expression was positively correlated with mRNA levels of histone demethylases (JMJD3 and UTX) and negatively correlated with gene expression of DNA methyltranferases. No such relationships were observed in subpopulations of healthy BM cells.
conclusionOur results demonstrate that specific molecular genetic aberrations, rather than differentiation per se, underlie the observed differences in HOX gene expression in AML. Moreover, the observed correlations between epigenetic modifiers and HOX expression that are specific to malignant hematopoiesis, suggest their potential causal relationships.
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