|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
We evaluated the function of Meningioma 1 (MN1), a cofactor of HOXA9 and MEIS1, in human and murine MLL-rearranged leukemia by CRISPR-Cas9 mediated deletion of MN1.
|
31413090 |
2019 |
|
Childhood Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
MEIS1 expression was also variable in a pediatric MLL-rearranged ALL patient dataset, highlighting the existence of a previously undescribed metabolic variability in MLL-rearranged leukemia that may contribute to the heterogeneity of the disease.
|
30670779 |
2019 |
|
Childhood Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
The homeobox transcription factor Meis1 is required for mammalian development, and its overexpression plays a role in tumorigenesis, especially leukemia.
|
29592525 |
2018 |
|
Childhood Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Using a global gene expression screen, we found that expression of Ednra was upregulated in murine leukemia inducing cells co-expressing Hoxa9 and Meis1 compared to cells only expressing Hoxa9.
|
30384975 |
2018 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Whether Meis1 functions independently of MLL abnormality in the context of leukemia is unclear.
|
28054140 |
2017 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Interaction of HOXA9/MEIS1/PBX3 is responsible for hematopoietic system transformation in MLL-rearranged (MLL-r) leukemia.
|
28411381 |
2017 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
|
28399410 |
2017 |
|
Childhood Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
To define the role of Flt3 in AML with high Hoxa9/Meis1, we treated mice with Hoxa9/Meis1-induced AML with the Flt3 inhibitor AC220, used an Flt3-ligand (FL-/-) knockout model, and investigated whether overexpression of Flt3 could induce leukemia together with overexpression of Hoxa9.
|
27617578 |
2017 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Although MEIS1 alone has only a moderate effect on cell proliferation in vitro, it is essential for the development of HOXA9-induced leukemia in vivo.
|
27018596 |
2016 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
We determined that HOXA9 and MEIS1 are coexpressed with MN1 in a subset of clinical MN1hi leukemia, and human MN1hi/HOXA9hi leukemias were sensitive to pharmacologic inhibition of DOT1L.
|
26927674 |
2016 |
|
Childhood Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Based on our previous work detecting high miR-155 levels in response to Meis1 overexpression in a murine Hox leukemia model, we show here the relationship among HOXA9, MEIS1, and miR-155 levels in MLL-translocated acute myeloid leukemia (AML) patients.
|
27619068 |
2016 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Here we establish the competitive relationship between PKNOX1 and MEIS1 in PBX-containing complex formation and determine the antagonistic role of PKNOX1 to leukemia in a murine MLL-AF9 model.
|
27123834 |
2016 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Finally, kinetics and severity of disease in transplantation assays indicated that Pbx3/Meis1 dimers are rate-limiting factors for Hoxa9-induced leukemia.
|
25911551 |
2015 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Hypoxia or HLF expression reversed the oxidative stress, rescuing leukemia development in Meis1-deficient cells.
|
25740828 |
2015 |
|
Childhood Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Aberrant activation of the three-amino-acid-loop extension homeobox gene MEIS1 shortens the latency and accelerates the onset and progression of acute leukemia, yet the molecular mechanism underlying persistent activation of the MEIS1 gene in leukemia remains poorly understood.
|
24022755 |
2014 |
|
Childhood Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Although high expression of Hoxa9 in MLL fusion leukemia is supposed to be responsible for the recruitment of EZH2, our data also suggest that there may be some other mechanisms independent of Hoxa9 activation to suppress p16 expression, because expression levels of Hoxa9 and p16 were not inversely related between MLL/ENL and Hoxa9/Meis1 transduced cells.
|
24612037 |
2014 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
We report that expression of the reactive oxygen species (ROS) scavenger glutathione peroxidase 3 (GPx3) positively correlates with the frequency of leukemia stem cells (LSCs) in Hoxa9+Meis1-induced leukemias.
|
22508837 |
2012 |
|
Childhood Leukemia
|
0.100 |
PosttranslationalModification
|
disease |
BEFREE |
Importantly, silencing of MEIS1 decreases the proliferation of leukemia-derived cells but increases their survival after etoposide treatment.
|
22185299 |
2011 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
The establishment of leukemia in transplantation recipients was significantly delayed by Meis1 knockdown.
|
19109563 |
2009 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
The most up-regulated genes include several HOX genes (e.g., HOX A5, HOXA9, and HOXA10) and MEIS1, which are the typical hallmark of MLL rearrangement leukemia.
|
19155294 |
2009 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Interestingly, an engineered NUP98-HOXA10 (NA10) fusion can induce a several hundred-fold expansion of HSCs in vitro and NA10 and the AML-associated fusion gene NUP98-HOXD13 (ND13) have a virtually indistinguishable ability to transform myeloid progenitor cells in vitro and to induce leukemia in collaboration with MEIS1 in vivo.
|
17712416 |
2007 |
|
Childhood Leukemia
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Though the resulting chimeric proteins directly participate in the development of leukemia, the long latency and monoclonal nature of the disease support the requirement for secondary mutation(s), such as those leading to overexpression of Meis1.
|
15744344 |
2005 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
Conversely, coexpression of the Hox cofactor Meis1 alleviated the requirement of a strong intrinsic Hox-transforming potential to induce leukemia.
|
14966272 |
2004 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
The MEIS1 homeobox protein forms a complex with the HOXA9 and PBX proteins that are implicated in human leukemia.
|
11161815 |
2001 |
|
Childhood Leukemia
|
0.100 |
Biomarker
|
disease |
BEFREE |
To gain a further understanding of the role Meis1 plays in leukemia and development, as well as to identify conserved regions of the protein that might reveal function, we cloned and characterized Mrgs from the mouse and human genomes.
|
9049632 |
1997 |