The advances of modern biomedical sciences through sequencing of the human genome, improvements in the methods of protein and nucleic acids analysis, and synthesis of drug libraries through combinatorial chemistry, opened intriguing possibilities for a better understanding, diagnosis and treatment of cancer. Here we investigated some potential target genes associated with the bone marrow (BM) microenvironment of childhood acute lymphoblastic leukemia (ALL). Interaction of leukemia cells with BM microenvironment contributes for acquisition of proliferative advantages by leukemia cells. To identify microenvironment genes modulated by leukemia, we stimulated BM stromal cells by co-culturing them with primary leukemia cells or by addition of ALL patient's plasma to the culture medium; and then performed microarray analysis. Leukemia-induced expression of these candidate stromal genes, and other candidates genes from the literature, was evaluated by quantitative RT-PCR analysis. STC1 was among the genes that showed, in vitro, higher levels of activation by leukemia, and thus was chosen for further functional and structural analyses. This up-regulation will be validated by immunohistochemical expression analysis in BM biopsies from ALL patients or normal donors. STC1 is an endocrine hormone originally discovered in bony fishes but also identified in mammals where is widely expressed in various tissues but neither its receptor nor its exact functions are known. Evidences suggest that STC1 altered expression could be involved in human cancer. STC1 cDNA was amplified from cells from healthy BM stromal cells and cloned into vectors for heterologous protein expression and yeast two-hybrid assays. STC1 protein showed insoluble expression in bacteria but was expressed in soluble form in the baculovirus system. We are currently optimizing the purification for both crystallization trials and spectroscopic assays. Simultaneously, yeast two-hybrid system is being used to screen a human fetal brain cDNA library for interacting proteins.