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The RET receptor tyrosine kinase, but not its specific ligand, GDNF, is preferentially expressed by acute leukaemias of monocytic phenotype and is up‐regulated upon differentiation
Author(s) -
Gattei Valter,
Degan Massimo,
Rossi Francesca Maria,
De Iuliis Angela,
Mazzocco Francesca Tassan,
Cesa Emiliana,
Aldinucci Donatella,
Zagonel Vittorina,
Pinto Antonio
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1999.01285.x
Subject(s) - receptor tyrosine kinase , phenotype , glial cell line derived neurotrophic factor , tyrosine kinase , cancer research , receptor protein tyrosine kinases , receptor , ror1 , biology , microbiology and biotechnology , kinase , platelet derived growth factor receptor , genetics , gene , neurotrophic factors , growth factor
The RET gene product represents the signal‐transducing molecule of a surface receptor complex for the glial cell line‐derived neurotrophic factor (GDNF), which includes GDNFR‐α as a ligand‐binding component. By a semi‐quantitative competitive RT‐PCR approach, we have analysed the relative abundances of RET transcripts in blasts purified from 40 acute myeloid leukaemia (AML) cases, revealing significant amounts of RET transcripts in 60% of AML cases (24/40). RT‐PCR data was confirmed by immunocytochemical detection of RET protein in leukaemic blasts. The highest RET mRNA levels, almost exclusively confined to FAB M4/M5 AMLs, directly correlated with the presence on leukaemic cells of adhesion molecules and surface structures typically expressed by blasts of monocytic lineage and were inversely associated with the expression of the stem cell antigen CD34. Consistently, differentiation of the monoblastic cell line U937 resulted in an up‐regulated expression of RET proto‐oncogene, which was maximal upon exposure to agents inducing a more complete monocytic differentiation. Finally, while transcripts specific for GDNF and GDNFR‐α were never found in leukaemic blasts, stromal cells of the haemopoietic microenvironment expressed, in the absence of RET, significant amounts of both GDNF and GDNFR‐α. Our results suggest a role for RET in the functional regulation of AMLs through interactions with GDNF‐ and GDNFR‐α‐producing stromal cells.