In this study, we aimed to investigate the association between miR-181a and HOXA7, HOXA9, and HOXA11 and explore their roles in predicting prognosis in AML.
Genetic or pharmacologic targeting of one key member of this network, RBM39, repressed cassette exon inclusion and promoted intron retention within mRNAs encoding HOXA9 targets as well as in other RBPs preferentially required in AML.
The PAF1c is required for MLL fusion-driven acute myeloid leukemia (AML) through direct regulation of pro-leukemic target genes such as Hoxa9 and Meis1.
Overall, these data support the conclusion that HoxA9 represses Cebpa expression, at least in part via inhibition of its +8 kb enhancer, potentially allowing normal myeloid progenitors to maintain immaturity and contributing to the pathogenesis of acute myeloid leukemia associated with increased HOXA9.
Our data establish a direct link between drug responses and endogenous expression of JMJD1C and HOXA9 in human AML cell line- and patient-derived xenografts.
The additional overexpression of miR-155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells <i>in vivo</i> However, in the absence or following the removal of miR-155, leukemia onset and progression were unaffected.
Combined IRX3 and Hoxa9 expression in murine HSPCs impeded normal T-progenitor differentiation in lymphoid culture and substantially enhanced the morphologic and phenotypic differentiation block of AML in myeloid leukemia transplantation experiments through suppression of a terminal myelomonocytic program.
Protease knockout allowed the comprehensive determination of genome-wide HoxA9 binding sites by chromatin immunoprecipitation sequencing in primary murine cells and a human AML cell line.
We found that the expression of HMGA2 and HOXA9 was reduced during the process of granulo-monocytic maturation of acute myeloid leukaemia (AML) cells, knockdown of HMGA2 promotes terminal (granulocytic and monocytic) differentiation of myeloid leukaemia primary blasts and cell lines, and HOXA9 was significantly downregulated in leukaemic cells with knockdown of HMGA2.
We discovered that the CTCF binding site located between <i>HOXA7</i> and <i>HOXA9</i> genes (CBS7/9) is critical for establishing and maintaining aberrant <i>HOXA9-HOXA13</i> gene expression in AML.
Therefore, this work provided a promising and potentially efficient target to leukaemia treatment, indicating that HoxA9 is likely to be an ideal candidate in the gene therapy against acute myeloid leukaemia.
The chromosomal translocation t(7;11)(p15;p15) and the resulting nucleoporin 98-homeobox A9 (<i>NUP98-HOXA9</i>) gene fusion is rare but recurrent genetic abnormity in acute myeloid leukemia (AML).
Gene expression studies show that members of the HOX family of genes (HOXA9, 10, B3, B4 and PBX3) are highly upregulated in the AML from this mouse model as well as from primary human t(6;9) AML.
A poor prognosis subtype of acute myeloid leukemia (AML) is characterized by increased expression of a set of homeodomain (HD) transcription factors, including HoxA9, HoxA10 and Cdx4.