STEEL FACTOR AFFECTS SCL EXPRESSION DURING NORMAL ERYTHROID-DIFFERENTIATION

Steel factor is one of the growth factors that controls the proliferat ion and differentiation of hematopoietic cells and SCL, also known as Tcl-5 or Tal-1, if a transcription factor involved in erythropoiesis. In this report, we studied the role of SCL in the proliferation of hum an peripheral blood burst-forming unit-erythroid (BFU-E) and the effec ts of Steel factor on SCL expression in proliferating erythroid cells. BFU-E-derived colonies increase progressively in size, as determined by cell number, from day 7 to day 74 of culture, with the greatest inc rease in colony size (10-fold expansion) occurring between day 7 and d ay 10. SCL protein levels in BFU-E-derived cells were highest iri day 7 cells and decreased progressively from day 7 to day 14 of culture, s uggesting an association of SCL with erythroid proliferation. In contr ast, SCL mRNA levels did not decrease significantly between day 7 and day 14 cells, suggesting that posttranscriptional mechanisms are large ly responsible for the decrease in SCL protein observed. The role of S CL in Steel factor-induced erythroid proliferation was then examined. In BFU-E-derived colonies cultured with Steel factor, colony size was significantly increased compared to control. In day 7 and day 10 eryth roid precursors cultured with Steel factor, SCL protein was increased significantly compared to control. The increase in SCL protein levels in early erythroid precursors stimulated with Steel factor suggests on e mechanism through which Steel factor may enhance normal erythroid pr oliferation. SCL mRNA levels assessed by Northern blot in day 7 cells did not increase significantly in response to Steel factor stimulation , suggesting that posttranscriptional mechanisms may also be important in the increase in SCL protein observed in response to Steel. (C) 199 4 by The American Society of Hematology.