We have previously shown that HOXA9 collaborates with MEIS1 in the induction of acute myeloid leukemia (AML). In this report, we demonstrate that HOXB3, which is highly divergent from HOXA9, also genetically interacts with MEIS1, but not with PBX1, in generating AML.

Here we demonstrated that in the absence of coexpressed Hox genes, a dominant activating form of Meis1 (Vp16-Meis1) sustains self-renewal of undifferentiated hematopoietic progenitors that exhibit leukemic potential in vivo, functions that are not possessed by either wild-type Meis1 or the dominant repressive form of Meis1, en-Meis1.

2005年7月1日 · In this issue of Blood, Wang and colleagues have shed light on the molecular mechanisms whereby 2 homeobox genes—one oncogenic (Hoxa9) and one not (Meis1)—can collaborate to cause acute myelogenous leukemia (AML).

2022年5月27日 · Myeloid ecotropic virus insertion site 1 (MEIS1) is a HOX co-factor known to be necessary for normal hematopoiesis [1, 2] and it is implicated in a...

In this report, we demonstrate that HOXB3, which is highly divergent from HOXA9, also genetically interacts with MEIS1, but not with PBX1, in generating AML. In addition, we show that the HOXA9 and HOXB3 genes play key roles in establishing all the main characteristics of the leukemias, while MEIS1 functions only to accelerate the onset of the ...

Vp16-Meis1-mediated transformation required the Meis1 function of binding to Pbx and DNA but not its C-terminal domain (CTD). The absence of endogenous Hox gene expression in Vp16-Meis1-immortalized progenitors allowed us to investigate how Hox alters gene expression and cell biology in early hematopoietic progenitors.

2010年4月15日 · Pbx-depleted and meis1-morphant embryos exhibit normal posterior hox gene expression. Shown are representative embryos following in situ hybridization analyses of hoxb6b (A, B, G, H), hoxb7a (C, D, I, J), and hoxa9a (E, F, K, L) expression in wild type (WT; A, C, E, G, I, K), Pbx-depleted (B, D, F), and meis1 -morphant (H, J, L) embryos.

2017年4月10日 · In the context of Hoxa9 overexpression, Syk signaling induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.

In mammals the 39 class 1 homeobox, or HOX genes, are arranged into four parologous clusters (A, B, C and D) on separate chromosomes (3, 4). In addition to their role in regulating development, a subset of A and B cluster HOX genes also play crucial roles in regulating hematopoiesis and leukemogenesis (5–7).

2024年11月5日 · The selective binding of HOX proteins to DNA is influenced by interactions with cofactors, most notably the MEIS family. While the regulation of HOX genes in certain AML subsets is well-characterized, the clinical and molecular profiles of patients with varying levels of HOX and MEIS interaction and expression are not fully understood.