The bone marrow microenvironment regulates early B lymphopoiesis and protects 
leukemia cells against chemotherapy treatment, thus the microenvironment may 
serve as a sanctuary site for these cells. Yet, few factors that contribute to 
this process are known. We have explored the role of transforming growth factor 
beta (TGFbeta) and bone morphogenetic protein-6 (BMP-6) and one target gene, 
TGFbeta inducible early gene 1 (TIEG1), in the communication between stroma 
cells and acute lymphoblastic leukemia (ALL) cell lines and their escape from 
chemotherapy. Here, we have demonstrated TIEG1 expression in both normal B 
progenitor cells and ALL cells, which increased rapidly upon TGFbeta and BMP-6 
treatment. Stimulation with TGFbeta or BMP-6, as well as overexpression of TIEG1 
inhibited proliferation. Furthermore, interaction with stroma cells induced 
TIEG1 expression in ALL cells, inhibited their proliferation and protected the 
cells against chemotherapeutic treatment. Similarly, treatment with TGFbeta or 
BMP-6, as well as overexpression of TIEG1, protected ALL cells against 
chemotherapy-induced cell death. These data suggest that TGFbeta and BMP-6 in 
the bone marrow microenvironment allow leukemia cells to escape therapy. 
Further, the data indicate that TIEG1 might be involved in mediating this effect 
from the microenvironment onto the leukemia cells.