Anti-CHRDL1 (aa 347-456) polyclonal antibody

In T-cell acute lymphoblastic leukemia (T-ALL), several members of the NK-like (NKL) homeobox genes are aberrantly expressed. Here, we have analyzed the activity of NKL homeobox gene MSX1 using pediatric T-ALL in silico data, detecting overexpression in 11% of patients. Quantifi cation of MSX1 transcripts in a panel of 24 T-ALL cell lines demonstrated overexpression in two examples. Comparative expression profiling indicated inhibition of the bone morphogenetic protein (BMP) signaling pathway, which was shown to inhibit MSX1 transcription. In the LOUCY cell line we identified conspicuous expression of CHRDL1 encoding a BMP inhibitor which mediated activation of MSX1. Promoter analyses demonstrated activation of CHRDL1 by oncogenic PITX1. Furthermore, knockdown and overexpression studies of hematopoietic transcription factors demonstrated that GATA2 and FOXC1 mediate activation and GATA3, LEF1, TAL1 and TOX repression of MSX1 transcription. Collectively, our findings suggest that MSX1 is physiologically restricted to lymphoid progenitors. The identification of deregulated BMP signaling may provide novel therapeutic options for the treatment of T-ALL.

In the present study, the effects of chordin-like protein 1 (CHRDL1) overexpression, together with bone morphogenetic protein-4 (BMP-4) treatment, on the differentiation of rat spinal cord-derived neural stem cells (NSCs) was investigated. Adult rat spinal cord-derived NSCs were cultured in serum-free medium. The recombined eukaryotic expression vector pSecTag2/Hygro B-CHRDL1 was transfected into adult rat spinal cord-derived NSCs using a lipid-based transfection reagent and protein expression was assessed by western blot analysis. Differentiation of transfected NSCs following BMP-4 treatment was determined by immunocytochemistry. The percentage of microtubule-associated protein-2 (MAP-2)-positive cells in the BMP-4-treated (B) group was found to be significantly lower compared with that in the non-transfected control (N) group. The percentage of MAP-2-positive cells in the pSecTag2/Hygro B-CHRDL1-transfected, BMP-4-treated group was identified to be significantly higher compared with that in group B, however, no significant difference was observed between group N and the transfected, non-BMP-4-treated control group. The current study indicates that CHRDL1 protein antagonizes BMP-4 activity and induces spinal cord-derived NSCs to differentiate into neurons.