ArticleOncotarget2016
The IRX1/HOXA connection: insights into a novel t(4;11)- specific cancer mechanism.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- BUB1-based risk model predicts prostate cancer prognosis and reveals therapeutic vulnerabilities.European journal of medical research · 2025Article
- Aberrant stem cell and developmental programs in pediatric leukemia.Frontiers in cell and developmental biology · 2024Review
- Review
- Normal and Aberrant TALE-Class Homeobox Gene Activities in Pro-B-Cells and B-Cell Precursor Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2022Article
- The immune checkpoint ICOSLG is a relapse-predicting biomarker and therapeutic target in infant t(4;11) acute lymphoblastic leukemia.iScience · 2022Article
- The Hematopoietic TALE-Code Shows Normal Activity of IRX1 in Myeloid Progenitors and Reveals Ectopic Expression of IRX3 and IRX5 in Acute Myeloid Leukemia.International journal of molecular sciences · 2022Article
- Genome-wide aberrant methylation in primary metastatic UM and their matched metastases.Scientific reports · 2022Article
- A human fetal liver-derived infant MLL-AF4 acute lymphoblastic leukemia model reveals a distinct fetal gene expression program.Nature communications · 2021Article
- Epigenetic Control of Infant B Cell Precursor Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2021Review
- Epigenetic Inactivation of the Tumor SuppressorCancers · 2020Article
- Prognostic value of Iroquois homeobox 1 methylation in non-small cell lung cancers.Genes & genomics · 2020Article
- Enhanced hemato-endothelial specification during human embryonic differentiation through developmental cooperation betweenHaematologica · 2019Article
- Another piece of the puzzle added to understand t(4;11) leukemia better.Haematologica · 2019Article
- Unraveling the cellular origin and clinical prognostic markers of infant B-cell acute lymphoblastic leukemia using genome-wide analysis.Haematologica · 2019Article
- A novel small molecule that kills a subset of MLL-rearranged leukemia cells by inducing mitochondrial dysfunction.Oncogene · 2019Article
- Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One hallmark of MLL-r leukemia is the highly specific gene expression signature indicative for commonly deregulated target genes. An usual read-out for this transcriptional deregulation is the HOXA gene cluster, where upregulated HOXA genes are detected in MLL-r AML and ALL patients. In case of t(4;11) leukemia, this simple picture becomes challenged, because these patients separate into HOXAhi- and HOXAlo-patients. HOXAlo-patients showed a reduced HOXA gene transcription, but instead overexpressed the homeobox gene IRX1. This transcriptional pattern was associated with a higher relapse rate and worse outcome. Here, we demonstrate that IRX1 binds to the MLL-AF4 complex at target gene promotors and counteract its promotor activating function. In addition, IRX1 induces transcription of HOXB4 and EGR family members. HOXB4 is usually a downstream target of c-KIT, WNT and TPO signaling pathways and necessary for maintaining and expanding in hematopoietic stem cells. EGR proteins control a p21-dependent quiescence program for hematopoietic stem cells. Both IRX1-dependend actions may help t(4;11) leukemia cells to establish a stem cell compartment. We also demonstrate that HDACi administration is functionally interfering with IRX1 and MLL-AF4, a finding which could help to improve new treatment options for t(4;11) patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.