The SCL/tal gene codes for a member of the basic helix-loop-helix (bHLH) family of putative transcriptional regulators. This gene was discovered by virtue of its association with a t(1;14) (p32;qll) chromosomal translocation found in cases of T cell acute lymphoblastic leukemia (T-ALL). Our long-term goal is to extend our initial studies regarding the expression and function of SCL/tal in hematopoietic tissues. We intend to undertake a careful evaluation of SCL/tal mRNA expression by studying additional tumor cell lines. Several nonhematopoietic lines will also be studied to evaluate the possibility of nonhematopoietic expression. We will detect expression of SCL-tal protein by protein blotting or fluorescence microscopy using an SCL/tal polyclonal rabbit antiserum recently developed in our laboratory. Two color fluorescence will be used to determine the phenotype of hematopoietic cells expressing the SCL/tal protein. Expression of SCL/tal during mammalian development will be evaluated using a transgenic mouse model incorporating a SCL/tal promoter fused to coding sequences of the bacterial beta-galactosidase gene, Lac Z. Functional studies of SCL/tal include analysis of stable clonal transfectants of K562 cells with a construct, Id-SCL/tal, designed to antagonize the DNA binding function of SCL/tal. The growth and phenotypic characteristics of these transfectants will be compared with controls. Additional studies in transgenic mice will include analysis of the consequences of ectopic SCL/tal expression under the control of the central nervous system-specific promoter from the rhombotin gene, as well as constructs designed to antagonize (Id-SCL/tal) or augment SCL/tal expression in T cells. Data regarding expression and function of SCL/tal will enhance understanding of how transcriptional regulators influence hematopoiesis and associated pathologic conditions such as leukemia and lymphoma.
| Dai, W; Pan, H Q; Ouyang, B et al. (1996) Expression of receptor protein tyrosine kinase tif is regulated during leukemia cell differentiation. Leukemia 10:978-83 |
