Abnormalities of the P53, MDM2, BCL2 and BAX genes in acute leukemias.
Abnormalities of the P53 network have been implicated in the pathogenesis of acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML). The purpose of this study was to define P53 gene mutations, to detect MDM2 gene amplification and to estimate mRNA expression of P53, MDM2, BCL2 and BAX genes in patients with ALL and AML. Twenty-five patients with ALL and 65 patients with AML, both recently diagnosed, were included into this study. Exons 5-8 of the P53 gene with flanking intronic sequence were amplified by the polymerase chain reaction (PCR) method and subjected to mutation screening by single-strand conformation polymorphism analysis (SSCP). Mutation of the P53 gene was found in one patient of the 25 with ALL and in five patients of the 65 with AML. Sequence analysis was subsequently performed. One mutation in intronic sequence in ALL and four missense mutations and one silent nucleotide substitution in AML were identified. Amplification of MDM2 gene was detected by multiplex-PCR analysis in only one sample from patient with ALL, but was not observed in any case of AML. To gain further insight into the role of P53 network in the evolution of acute leukemias, the P53, MDM2, BCL2 and BAX mRNAexpressions in portion samples from patients with ALL and AML were analyzed using multiplex RT-PCR. Although a low frequency of molecular disturbances of the P53 and the MDM2 genes was detected in this study, there was a high percentage of cases with increased mRNA level of P53 and MDM2. A high frequency of BCL2 mRNA overexpression and a relatively low frequency of BAX mRNA overexpression detected in both analyzed leukemias in this study, indicate that altered transcription of these genes may be involved in leukemogenesis.
Wojcik
I
I
Department of Molecular Pathology and Neuropathology, Chair of Oncology, Medical University of Lodz, 92-216 Lodz, Poland. i-wojcik@wp.pl
Szybka
M
M
Golanska
E
E
Rieske
P
P
Blonski
J Z
JZ
Robak
T
T
Bartkowiak
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D019254:Genes, bcl-2; D016158:Genes, p53; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2