PTEN deficiency is a common defect in juvenile myelomonocytic leukemia.
The biological hallmark of juvenile myelomonocytic leukemia (JMML) is selective GM-CSF hypersensitivity. We hypothesized that PTEN protein deficiency might lead to insufficient negative growth signals to counter the hyperactive Ras signaling and therefore aid in the acceleration of the malignant transformation of JMML. In screening 34 JMML patients we found: (1) decreased PTEN protein in 67% of patients; (2) significantly lower PTEN mRNA levels in patients compared to controls (p<0.01); (3) a hypermethylated PTEN promoter in 77% of patients; and (4) constitutive-hyperactive Akt and MAPK in 55% and 73% of patients, respectively. These findings suggest that PTEN deficiency is very common in JMML and is in part due to hypermethylation of the PTEN gene promoter.
Liu
Yunying Lucy
YL
Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, 4301 West Markham Street, slot #623, Little Rock, AR 72205-7199, USA.
Castleberry
Robert P
RP
Emanuel
Peter D
PD
D001483:Base Sequence; D015153:Blotting, Western; D019175:DNA Methylation; D017931:DNA Primers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D054429:Leukemia, Myelomonocytic, Juvenile / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology; D014158:Transcription, Genetic
D017931:DNA Primers; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011494:Protein Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D020123:Sirolimus