Frequency and prognostic significance of murine double minute protein-2 overexpression and p53 gene mutations in childhood acute lymphoblastic leukemia.
OBJECTIVE
Determination of frequency and prognostic significance of murine double minute protein-2 (MDM-2) over expression and its association with p53 status in children with acute lymphoblastic leukemia (ALL).


METHODS
MDM-2 expression by flow cytometry and p53 gene status by PCR were determined in peripheral blood or bone marrow of 46 ALL children (at initial diagnosis) and control group.


RESULTS
MDM-2 was significantly overexpressed in 15 patients (32.6%). p53 mutation was detected in six out of 46 patients at initial diagnosis, three of them were out of 29 cases achieving complete remission (CR) and the other three cases were out of 17 of relapsed patients, which is significantly higher than CR group (P<0.05). Positive correlation was found between the MDM-2 overexpression and initial WBCs count, peripheral blast cell count and presence of CNS blasts (P<0.05, <0.05 and <0.05 respectively).


CONCLUSIONS
MDM-2 is overexpressed in a significant number of childhood ALL, and more often observed in the poor outcome group and its frequency is not related to p53 status. Measurement of MDM-2 as a bad prognostic marker even in cases with non-mutant p53 is very important. Moreover, MDM-2 may be a potential molecular target for production of new cancer therapy.
Hendy
Olfat M
OM
Clinical Pathology Department, (National Liver Institute), Menoufiya University, Egypt.
Elghannam
Doaa M
DM
El-Sharnouby
Jehan A
JA
Goda
Enas F
EF
El-Ashry
Rasha
R
Al-Tonbary
Youssef
Y
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001752:Blast Crisis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis* / Q000235:genetics; D012008:Recurrence; D012074:Remission Induction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2