AHI-1: a novel signaling protein and potential therapeutic target in human leukemia and brain disorders.

Progress in the understanding of the molecular and cellular mechanisms of human cancer, including human leukemia and lymphomas, has been spurred by cloning of fusion genes created by chromosomal translocations or by retroviral insertional mutagenesis; a number of oncogenes and tumor suppressors involved in development of a number of malignancies have been identified in this manner. The BCR-ABL fusion gene, originating in a multipotent hematopoietic stem cell, is the molecular signature of chronic myeloid leukemia (CML). Discovery of this fusion gene has led to the development of one of the first successful targeted molecular therapies for cancer (Imatinib).

Up-regulation of metallothionein gene expression in parkinsonian astrocytes.

The role of glial cells in Parkinson's disease (PD) is unclear. We have previously reported a striking up-regulation of DnaJB6 heat shock protein in PD substantia nigra astrocytes. Whole genome transcriptome analysis also indicated increased expression of metallothionein genes in substantia nigra and cortex of sporadic PD cases.

Identification of tyrosine kinase, HCK, and tumor suppressor, BIN1, as potential mediators of AHI-1 oncogene in primary and transformed CTCL cells.

AHI-1 is an oncogene often targeted by provirus insertional mutagenesis in murine leukemias and lymphomas. Aberrant expression of human AHI-1 occurs in cutaneous T-cell lymphoma (CTCL) cells and in CD4(+)CD7(-) Sezary cells from patients with Sezary syndrome. Stable knockdown of AHI-1 using retroviral-mediated RNA interference in CTCL cells inhibits their transforming activity in vitro and in vivo.