We found that SOCS5 was differentially expressed in primary T-ALL and its expression levels were lowered in HOXA-deregulated leukemia harboring KMT2A gene rearrangements.
Elevated expression of HOXA genes is critical for leukemia maintenance and progression; however, the precise mechanism by which CALM-AF10 alters HOXA gene expression is unclear.
Together the data support a key role for HOXA/TALE in cytogenetically normal acute myeloid leukemia and demonstrate that targeting of clinically significant HOXA/PBX3 elements may provide therapeutic benefit to patients with this subtype of leukemia.
Collectively, our data suggest that PBX3 is a critical cofactor of HOXA9 in leukemogenesis, and targeting their interaction is a feasible strategy to treat presently therapy resistant CA-AML (eg, MLL-rearranged leukemia) in which HOXA/PBX3 genes are overexpressed.
This review discusses the normal structure and function of CALM and AF10, describes the spectrum of clinical findings seen in patients with CALM-AF10 fusions, summarizes recently published CALM-AF10 mouse models and highlights the role of HOXA cluster gene activation in CALM-AF10 leukemia.
HOXA6 hypermethylation was predominantly restricted to lymphoid malignancies, whereas hypermethylation of other HOXA and HOXB genes was only observed in childhood leukemia.
We have analyzed the expression pattern of the entire HOX 1 locus in a panel of leukemia-derived human cell lines representing various blood phenotypes.