We show that TRIB1-TRIB2 display a significant negative correlation in myelodysplastic syndrome and acute myeloid leukemia (AML) subtypes, but not in acute lymphoid leukemia.
A higher expression ratio of Trib1 to MLF1 was a key determinant for AML development in mouse models, which was also confirmed in human patient samples with acute leukemia.
TRIB1 is also involved in a certain type of human AML and a TRIB1 somatic point mutation R107L was identified in a case of Down syndrome (DS)-related acute megakaryocytic leukaemia.
Murine bone marrow transplantation experiments showed that coexpression of COP1 accelerates development of acute myeloid leukemia induced by Trib1, which pathologically resembles that of p42C/EBPα-deficient mice.
Increased Trib1 and Trib2 mRNA expression occurs in human myeloid leukemia and induces acute myeloid leukemia in mice, whereas Trib3 has not been associated with leukemia.
These results exclude MYC as the target gene and indicate that overexpression of C8FW may be the functionally important consequence of 8q24 amplicons in AML and MDS.