scholarly journals Mutations of the p53 gene in myelodysplastic syndrome (MDS) and MDS- derived leukemia

Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 3022-3026 ◽  
Author(s):  
K Sugimoto ◽  
N Hirano ◽  
H Toyoshima ◽  
S Chiba ◽  
H Mano ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Point Mutations ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
Nucleotide Sequencing ◽  
Polymorphism Analysis ◽  
P53 Gene Mutation ◽  
Ras Gene ◽  
P53 Gene Mutations

Abstract The p53 gene is currently thought to be a tumor suppressor gene, and its alterations have been suggested to be involved in the pathogenesis of several human malignancies, including some leukemias and lymphomas. We present here evidence for the possible involvement of p53 gene mutations in the myelodysplastic syndrome (MDS), although the incidence is relatively low. Forty-four patients with MDS and six patients with overt leukemias that developed from MDS were studied for p53 gene alterations using reverse transcriptase-polymerase chain reaction, single-strand conformation polymorphism analysis, and nucleotide sequencing. Three patients with MDS (2 RAEB and 1 RAEB in T) had missense point mutations in the conserved regions of the p53 coding sequence. Furthermore, expression of the wild-type p53 mRNA was not detected in these three patients. The probable absence of normal p53 function in the three cases studied here suggests that alterations in the p53 gene may occasionally play a role in MDS. These three MDS patients with p53 gene mutations and an MDS-derived erythroleukemia cell line that we had previously reported to carry a p53 gene mutation showed no N-ras gene mutations, suggesting heterogeneity in the oncogenic mechanism of MDS.

scholarly journals Mutations of the p53 gene in myelodysplastic syndrome (MDS) and MDS- derived leukemia

Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 3022-3026 ◽  
Author(s):  
K Sugimoto ◽  
N Hirano ◽  
H Toyoshima ◽  
S Chiba ◽  
H Mano ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Point Mutations ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
Nucleotide Sequencing ◽  
Polymorphism Analysis ◽  
P53 Gene Mutation ◽  
Ras Gene ◽  
P53 Gene Mutations

The p53 gene is currently thought to be a tumor suppressor gene, and its alterations have been suggested to be involved in the pathogenesis of several human malignancies, including some leukemias and lymphomas. We present here evidence for the possible involvement of p53 gene mutations in the myelodysplastic syndrome (MDS), although the incidence is relatively low. Forty-four patients with MDS and six patients with overt leukemias that developed from MDS were studied for p53 gene alterations using reverse transcriptase-polymerase chain reaction, single-strand conformation polymorphism analysis, and nucleotide sequencing. Three patients with MDS (2 RAEB and 1 RAEB in T) had missense point mutations in the conserved regions of the p53 coding sequence. Furthermore, expression of the wild-type p53 mRNA was not detected in these three patients. The probable absence of normal p53 function in the three cases studied here suggests that alterations in the p53 gene may occasionally play a role in MDS. These three MDS patients with p53 gene mutations and an MDS-derived erythroleukemia cell line that we had previously reported to carry a p53 gene mutation showed no N-ras gene mutations, suggesting heterogeneity in the oncogenic mechanism of MDS.

scholarly journals P53 gene mutations in acute myeloid leukemia with 17p monosomy

Blood ◽  
1991 ◽  
Vol 78 (7) ◽  
pp. 1652-1657 ◽  
Author(s):  
P Fenaux ◽  
P Jonveaux ◽  
I Quiquandon ◽  
JL Lai ◽  
JM Pignon ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
Nucleotide Sequencing ◽  
Polymorphism Analysis ◽  
Cytogenetic Abnormalities ◽  
P53 Gene Mutations ◽  
Acute Myeloid

Abstract We looked for mutations of exons 5 to 8 of the P53 gene in 10 patients with acute myeloid leukemia (AML) and 17p monosomy, and 36 patients with AML and no cytogenetic abnormalities of 17p. DNA was analyzed by polymerase chain reaction, single-strand conformation polymorphism analysis, and nucleotide sequencing. Four of the 10 patients with 17p monosomy showed point mutation, single-nucleotide deletion, or insertion in exons 7 or 8. By contrast, only 1 of the 36 patients with AML and no cytogenetic abnormalities of 17p showed a mutation of the P53 gene in exons 5 to 8 (P less than .01). These results suggest that alterations of the P53 gene may have a role in leukemogenesis in some cases of AML. The fact that P53 gene mutations occurred more often in patients with 17p monosomy seems to support the “recessive” model of tumor suppressive activity of the P53 gene rather than the “dominant” model, in which alteration of only one allele is sufficient for the development of malignancy.

scholarly journals P53 gene mutations in acute myeloid leukemia with 17p monosomy

Blood ◽  
1991 ◽  
Vol 78 (7) ◽  
pp. 1652-1657 ◽  
Author(s):  
P Fenaux ◽  
P Jonveaux ◽  
I Quiquandon ◽  
JL Lai ◽  
JM Pignon ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
Nucleotide Sequencing ◽  
Polymorphism Analysis ◽  
Cytogenetic Abnormalities ◽  
P53 Gene Mutations ◽  
Acute Myeloid

We looked for mutations of exons 5 to 8 of the P53 gene in 10 patients with acute myeloid leukemia (AML) and 17p monosomy, and 36 patients with AML and no cytogenetic abnormalities of 17p. DNA was analyzed by polymerase chain reaction, single-strand conformation polymorphism analysis, and nucleotide sequencing. Four of the 10 patients with 17p monosomy showed point mutation, single-nucleotide deletion, or insertion in exons 7 or 8. By contrast, only 1 of the 36 patients with AML and no cytogenetic abnormalities of 17p showed a mutation of the P53 gene in exons 5 to 8 (P less than .01). These results suggest that alterations of the P53 gene may have a role in leukemogenesis in some cases of AML. The fact that P53 gene mutations occurred more often in patients with 17p monosomy seems to support the “recessive” model of tumor suppressive activity of the P53 gene rather than the “dominant” model, in which alteration of only one allele is sufficient for the development of malignancy.

scholarly journals Mutations of the p53 gene in lymphoid leukemia

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1153-1156 ◽  
Author(s):  
K Sugimoto ◽  
H Toyoshima ◽  
R Sakai ◽  
K Miyagawa ◽  
K Hagiwara ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
Suppressor Gene ◽  
Nucleotide Sequencing ◽  
Polymorphism Analysis ◽  
Coding Region ◽  
Lymphoid Leukemia ◽  
Nucleotide Insertion

Abstract p53 is currently considered to be a tumor suppressor gene product, and its alterations are suggested to be involved in several human malignancies. Here we show evidence of the possible involvement of p53 gene mutations in lymphoid leukemias studied by reverse transcriptase- polymerase chain reaction, single strand conformation polymorphism analysis, and nucleotide sequencing. Fourteen patients with various leukemias were examined and two with acute lymphoblastic leukemia and one with Waldenstrom's macroglobulinemia were identified to have mutations in the coding region of the p53 gene. These mutations included point mutation, triplet deletion, and single nucleotide insertion. Furthermore, expression of the wild-type p53 mRNA was not detected in the samples from these three patients. In one of them, chromosome 17p was deleted, suggesting the absence of the nonmutated p53 gene, whereas in the other two patients, chromosome 17p seemed to be intact by cytogenetic analysis. Our results suggest that alterations of the p53 gene may have a role in the genesis of some leukemias.

scholarly journals p53 gene mutations in multiple myeloma are associated with advanced forms of malignancy

Blood ◽  
1993 ◽  
Vol 81 (1) ◽  
pp. 128-135 ◽  
Author(s):  
A Neri ◽  
L Baldini ◽  
D Trecca ◽  
L Cro ◽  
E Polli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Direct Sequencing ◽  
Point Mutations ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
P53 Mutation ◽  
Late Event ◽  
Multistep Process ◽  
P53 Gene Mutations

Abstract The frequency and type of p53 gene mutations was investigated in a series of 52 cases of multiple myeloma (MM) representative of the different clinical phases and forms of the disease (indolent, 12 cases; chronic, 24 cases; acute/leukemic, 16 cases). DNAs were analyzed for p53 gene mutations in exons 5 to 9 by polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct sequencing of PCR-amplified fragments. Point mutations were detected in 7 of 52 patients (13%) (5 at exon 8; 1 at exon 6; 1 at exon 7), and were specifically associated with the more advanced and clinically aggressive acute/leukemic forms of MM (7 of 16 [43%].) Three of the mutated cases had been evaluated at clinical presentation in earlier phases of the disease (indolent or chronic) and were found to be negative for p53 mutation. Moreover, three patients with p53 mutation had not received chemotherapy at the time of investigation. These results support the notion that the development of MM is a multistep process and suggest that alterations in the p53 gene may represent an important late event in MM tumor progression.

scholarly journals p53 gene mutations in multiple myeloma are associated with advanced forms of malignancy

Blood ◽  
1993 ◽  
Vol 81 (1) ◽  
pp. 128-135 ◽  
Author(s):  
A Neri ◽  
L Baldini ◽  
D Trecca ◽  
L Cro ◽  
E Polli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Direct Sequencing ◽  
Point Mutations ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
P53 Mutation ◽  
Late Event ◽  
Multistep Process ◽  
P53 Gene Mutations

The frequency and type of p53 gene mutations was investigated in a series of 52 cases of multiple myeloma (MM) representative of the different clinical phases and forms of the disease (indolent, 12 cases; chronic, 24 cases; acute/leukemic, 16 cases). DNAs were analyzed for p53 gene mutations in exons 5 to 9 by polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct sequencing of PCR-amplified fragments. Point mutations were detected in 7 of 52 patients (13%) (5 at exon 8; 1 at exon 6; 1 at exon 7), and were specifically associated with the more advanced and clinically aggressive acute/leukemic forms of MM (7 of 16 [43%].) Three of the mutated cases had been evaluated at clinical presentation in earlier phases of the disease (indolent or chronic) and were found to be negative for p53 mutation. Moreover, three patients with p53 mutation had not received chemotherapy at the time of investigation. These results support the notion that the development of MM is a multistep process and suggest that alterations in the p53 gene may represent an important late event in MM tumor progression.

scholarly journals Mutations of the p53 gene in lymphoid leukemia

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1153-1156 ◽  
Author(s):  
K Sugimoto ◽  
H Toyoshima ◽  
R Sakai ◽  
K Miyagawa ◽  
K Hagiwara ◽  
...  
Keyword(s):  
Lymphoblastic Leukemia ◽  
Gene Mutations ◽  
P53 Gene ◽  
Single Strand Conformation Polymorphism ◽  
Suppressor Gene ◽  
Nucleotide Sequencing ◽  
Polymorphism Analysis ◽  
Coding Region ◽  
Lymphoid Leukemia ◽  
Nucleotide Insertion

p53 is currently considered to be a tumor suppressor gene product, and its alterations are suggested to be involved in several human malignancies. Here we show evidence of the possible involvement of p53 gene mutations in lymphoid leukemias studied by reverse transcriptase- polymerase chain reaction, single strand conformation polymorphism analysis, and nucleotide sequencing. Fourteen patients with various leukemias were examined and two with acute lymphoblastic leukemia and one with Waldenstrom's macroglobulinemia were identified to have mutations in the coding region of the p53 gene. These mutations included point mutation, triplet deletion, and single nucleotide insertion. Furthermore, expression of the wild-type p53 mRNA was not detected in the samples from these three patients. In one of them, chromosome 17p was deleted, suggesting the absence of the nonmutated p53 gene, whereas in the other two patients, chromosome 17p seemed to be intact by cytogenetic analysis. Our results suggest that alterations of the p53 gene may have a role in the genesis of some leukemias.

scholarly journals p53 gene mutation in B-cell chronic lymphocytic leukemia is associated with drug resistance and is independent of MDR1/MDR3 gene expression

Blood ◽  
1993 ◽  
Vol 82 (11) ◽  
pp. 3452-3459 ◽  
Author(s):  
S el Rouby ◽  
A Thomas ◽  
D Costin ◽  
CR Rosenberg ◽  
M Potmesil ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Gene Mutations ◽  
P53 Gene ◽  
Lymphocytic Leukemia ◽  
P53 Mutations ◽  
P53 Gene Mutation ◽  
P53 Gene Mutations ◽  
Cell Chronic Lymphocytic Leukemia

We studied 53 patients with B-cell chronic lymphocytic leukemia (B-CLL) and found mutations of the p53 gene in 15%. Patients with p53 gene mutations were found to have an aggressive form of B-CLL disease characterized by advanced Rai stage, rapid lymphocyte doubling time (LDT), and resistance to chemotherapy. While 27 of 29 treated patients (93%) without p53 mutations achieved a partial remission, only one of seven treated patients (14%) with p53 mutations achieved a partial remission (P = .00009). Adjusting for prognostic factors (age, sex, race, and Rai stage), patients with p53 gene mutations had a 13-fold greater risk of death than patients without p53 mutations (P = .013). In addition to examining the clinical relevance of p53 gene mutations in B-CLL, we investigated the possible role of p53 gene regulation in the expression of the multidrug resistance genes MDR1 and MDR3. We quantitated MDR1 and MDR3 mRNA expression by reverse transcription- polymerase chain reaction (RT-PCR). Expression of both the MDR1 and MDR3 genes was independent of p53 gene mutation or prior drug treatment, and did not predict for clinical response. Our findings indicate that p53 gene mutations in B-CLL are associated with a poor clinical outcome and may be a prognostic indicator for drug resistance.

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