Loss of nuclear expression of the p33(ING1b) inhibitor of growth protein in childhood acute lymphoblastic leukaemia.
OBJECTIVE
p33(ING1b) is a tumour suppressor protein involved in growth control and apoptosis. Suppression of p33(ING1b) expression is associated with the loss of cellular growth control and immortalisation, whereas its overexpression causes cell cycle arrest. Moreover, normal p33(ING1b) expression is essential for optimal function of p53. Acute lymphoblastic leukaemia (ALL) is the most common malignancy of childhood, accounting for one third of all childhood malignancies. A variety of cytogenetic abnormalities have been described but there is no single abnormality common to all cases. Deregulation of the TP53 pathway is a common genetic abnormality in human malignancies. However, TP53 mutations are uncommon in ALL. It is possible that alternative mechanisms of regulation of the TP53 apoptosis pathway, such as modulation of p33(ING1b) expression, may be important in ALL. The aim of this study was to assess the expression of p33(ING1b) in childhood ALL.


METHODS
One hundred and forty five patients with childhood ALL were investigated in this immunohistochemical study of the expression of p33(ING1b).


RESULTS
Loss of nuclear expression of p33(ING1b) was seen in 78% of cases. This was associated with increased cytoplasmic expression of the protein. Kaplan Meier survival analysis demonstrated a trend towards a better prognosis for patients with tumours that had lost nuclear p33(ING1b).


CONCLUSIONS
These results suggest that the loss of nuclear p33(ING1b) expression may be an important molecular event in the pathogenesis of childhood ALL.
Nouman
G S
GS
Pathology Department, Royal Victoria Infirmary, University of Newcastle, Queens Victoria Road, Newcastle upon Tyne, NE1 4PH, UK.
Anderson
J J
JJ
Wood
K M
KM
Lunec
J
J
Hall
A G
AG
Reid
M M
MM
Angus
B
B
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D005500:Follow-Up Studies; D016147:Genes, Tumor Suppressor; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D011379:Prognosis; D011506:Proteins / Q000378:metabolism*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins