Differential expression of the RET gene in human acute myeloid leukemia

The RET proto-oncogene product is a receptor tyrosine kinase representing t he signal-transducing molecule of a multi-subunit membrane receptor complex for at least two different types of transforming growth factor (TGF)-beta- related neurotrophic factors. We have previously shown that RET gene expres sion in acute myeloid leukemia (AML) occurs more frequently in AMLs display ing either a monocytic (FAB M4/M5) or intermediate-mature myeloid phenotype (FAB M2/M3) than in leukemias reflecting an earlier stage of myeloid diffe rentiation (FAB M0/M1). To further verify the association between RET expre ssion and the relative maturation stage of AML cells, we have performed a q uantitative estimation of relative abundances of RET transcripts among vari ous FAB subtypes of AMLs. By analyzing 13 AML samples and normal hematopoie tic cells through a competitive-quantitative RT-PCR approach, we were able to show that the relative levels of RET-specific mRNAs continuously increas e with blast cell maturation in human AML, i.e., the amounts of RET gene-sp ecific transcripts differ among RET-expressing AMLs, being higher in the mo re differentiated FAB phenotypes. In addition, we provide evidence that the relative amounts of RET transcripts increase upon in vitro and in vivo dif ferentiation of leukemic promyelocytes from FAB M3 AML patients, becoming o verall comparable to those found in normal granulocytes. These results indi cate that RET expression in human AMLs is maturation-associated, probably m irroring the developmental regulation of this gene during differentiation o f normal hematopoietic cells.