Dec 18, 2019 · By tracking de novo transformation from normal hematopoietic progenitors expressing an acute myeloid leukemia (AML) oncogene MLL-AF9, we reveal that the cell cycle rate heterogeneity among...

We recently showed that cellular origin impacts the aggressiveness and the phenotype of acute myeloid leukemia (AML). Direct induction of the MLL-AF9 fusion in various hematopoietic compartments in vivo using a doxycycline (DOX) regulated mouse ...

Jul 11, 2016 · MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSC) in vitro resulted in dispersed clonogenic growth and expression of genes involved in migration and invasion.

Jul 11, 2016 · MLL-AF9 expression in long-term hematopoietic stem cells (LT-HSC) in vitro resulted in dispersed clonogenic growth and expression of genes involved in migration and invasion.

Jan 23, 2017 · In order to define a core set of MLL rearranged targets, we investigated the genome-wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and associated epigenetic signatures in acute...

By tracking de novo transformation from normal hematopoietic progenitors expressing an acute myeloid leukemia (AML) oncogene MLL-AF9, we reveal that the cell cycle rate heterogeneity among granulocyte–macrophage progenitors (GMPs) determines their …

In a study of target cells and oncogene dosage, we found that Mll-AF9, when under endogenous regulatory control, efficiently transformed LSK (Lin − Sca1 + c-kit +) stem cells while committed granulocyte-monocyte progenitors (GMPs) were transformation-resistant and …

Aug 1, 2024 · In this study, we investigated not only the relationship between MLL1 and AF9, the most frequent fusion partner of MLL1 in AML, and the role of AF9 in transcriptional regulation in the non-MLLr HEL cells, but also the chromatin occupancy patterns of MLL1 and MLL-AF9, and the role of MLL-AF9 in transcriptional regulation in MLL cells.

Stavropoulou et al. show that MLL-AF9 expression in mouse long-term hematopoietic stem cells causes invasive, chemoresistant acute myeloid leukemia (AML) that expresses genes related to epithelial-mesenchymal transition (EMT). Expression of EMT-related genes in human AML is associated with poor patient survival.

Mixed lineage leukemia-fusion proteins (MLL-FPs) are believed to maintain gene activation and induce MLL through aberrantly stimulating transcriptional elongation, but the underlying mechanisms are incompletely understood. Here, we show that both MLL1 and AF9, one of the major fusion partners of MLL …

Feb 17, 2010 · We demonstrate a crucial role for WT MLL, the common WT precursor of over 60 distinct MLL-FPs, in MLL-AF9-induced leukemogenesis. WT MLL influences MLL-AF9-induced histone methylation and gene expression as well as growth and survival of …

Our data demonstrated that RA pathway was more profoundly impaired in MLL-AF4/AF5q31 positive cells than MLL-AF9 positive cells, suggesting type of MLL fusion protein contributes inactivation of RA pathway. Our data also identified the sensitivity of ATRA was correlated with the ratio of H3K4me2/ H3 on the RARα promoter, and TCP restore the ...

Oct 26, 2016 · To circumvent the genetic heterogeneity of AML patient cohorts, we have developed a model system, driven by the MLL-AF9 (MA9) oncogene, to generate multiple human leukemias using progenitor cells...

May 12, 2016 · Retroviral transduction of fetal liver HSPCs and adult bone marrow with MLL-AF9 induces acute myeloid leukemia (AML); however, deletion of Id1 in fetal liver HSPCs significantly attenuates leukemogenesis, whereas deletion of Id1 in adult bone marrow HSPCs promotes leukemic development.

Jan 13, 2016 · MLL-AF9 (alias KMT2A-MLLT3) is a fusion gene resulting from the chromosomal translocation t (9;11) (p22;q23). It is sufficient to initiate acute leukemia in murine models [1, 2] and is the most frequent fusion gene in infant acute myeloid leukemia (AML) and especially associated with monoblastic AML (FAB-classification M5) [3, 4].

Mar 1, 2016 · Transformation by MLL-AF9 induces aberrant expression of a self-renewal–associated gene-expression program, which includes the canonical MLL-AF9 target genes homeobox A9 (HOXA9) and Meis homeobox 1 (MEIS1) (16–21).

Jun 8, 2017 · In order to define a core set of MLL rearranged targets, we investigated the genome-wide binding of the MLL-AF9 and MLL-AF4 fusion proteins and associated epigenetic signatures in acute myeloid leukemia (AML) cell lines THP-1 and MV4-11.

May 6, 2008 · In this study, we tested the ability of Mll-AF9, expressed under the control of the endogenous Mll promoter, to transform stem and progenitor cell populations and to produce leukemia in transplanted mice. Lethally irradiated WT mice received 25–2500 sorted Mll-AF9 HSC, CLP, CMP, or GMP cells.

Mar 16, 2017 · By generating a knock-in mouse model in which miR-125b overexpression is controlled by doxycycline induction, we demonstrated that miR-125b significantly enhances MLL-AF9 –driven AML in vivo, and the resultant leukemia is partially dependent on continued overexpression of miR-125b.

Feb 11, 2014 · MLL-AF9 is the most frequent fusion gene in infant AML and especially associated with monoblastic AML (M5) [9, 10]. New targeted therapies are needed for this type of leukemia with poor prognosis.