High FUS/TLS expression in acute myeloid leukaemia samples.
Retinoic acid has the ability to induce differentiation in some myeloid leukaemia cell lines and has been used to induce remission in acute promyelocytic leukaemia patients. We have analysed changes in gene expression, by differential display, in HL60 cells exposed to all-trans retinoic acid (ATRA) for only 1 h. Only about 0.4% of the genes examined by this technique showed changes in expression level, and all four of the gene fragments identified were downregulated during the short 1 h exposure. Two of the fragments were novel, a third was MYC and the fourth was the FUS proto-oncogene. Northern analysis showed that FUS was downregulated within 1 h only during induced neutrophil differentiation but not at all during induced monocyte differentiation. Unlike the sensitive cell lines, ATRA-resistant cell lines did not show a downregulation of FUS over a 24 h period of exposure to ATRA. Using a semiquantitative PCR analysis, no difference in FUS levels was observed between ATRA-sensitive and -resistant cell lines. A similar analysis was carried out on primary acute myeloid leukaemia (AML), peripheral stem cell harvests (PBSC) and cord blood samples. The PBSC and cord blood samples had FUS levels that were similar or generally less than the cell lines. However, much higher levels were seen in 63% of the AML samples examined. The data presented are consistent with previous reports for a role for FUS in the promotion and maintenance of cellular proliferation.
Mills
K I
KI
LRF Differentiation Programme, Department of Haematology, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Walsh
V
V
Gilkes
A F
AF
Sweeney
M C
MC
Mirza
T
T
Woodgate
L J
LJ
Brown
G
G
Burnett
A K
AK
D000208:Acute Disease; D002454:Cell Differentiation; D018922:HL-60 Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology
D034441:Heterogeneous-Nuclear Ribonucleoproteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins; D014212:Tretinoin