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Scientific comment on tumor suppressor p53 protein expression: prognostic significance in patients with low-risk myelodysplastic syndrome.

Velloso ED - Rev Bras Hematol Hemoter (2014)

View Article: PubMed Central - PubMed

Affiliation: Universidade de São Paulo (USP), São Paulo, SP, Brazil. Electronic address: elvira.velloso@yahoo.com.br.

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Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic neoplasms, characterized by dysplastic findings with variable degree of bone marrow failure and proliferation of blast cells... Factors related to the individual (such as performance status, co-morbidities, age and nutritional status), biological (severity of cytopenias, transfusion need, cytogenetic abnormalities, percentage of blasts, bone marrow fibrosis, primary or secondary disease) and social (access to health care and medications) impact the survival... The models most commonly used in prognostic score for MDS de novo, such as the International Prognostic Scoring System (IPSS), the WHO Prognostic Scoring System (WPSS), and the Revised International Prognostic Scoring System (IPSS-R) basically use biological variables, obtained from the study of blood cell counts (cytopenias), percentage of blasts in bone marrow aspirate and cytogenetic findings., , Recently, cytogenetic findings were better defined and cytogenetic abnormalities were divided into 5 risk groups, noting that the higher the complexity observed in the karyotype, the worst the survival is., Even in patients with normal karyotype, many genetic mutations described by molecular biology techniques have been associated with prognosis... The p53 gene (located at 17p13) is a tumor suppressor gene of great importance for genetic stability and integrity of the genome... DNA damage of several types activates the 53 kDa nuclear phosphoprotein p53 protein, resulting in cell cycle arrest at the G1 (post-mitotic phase) and G2 (pre-mitotic) cell cycle checkpoints necessary for DNA repair... The inactivation of the p53 gene in both alleles, loss of heterozygous (LOH), by mutations or deletions have been related to the predisposition to neoplastic transformation... The wild type gene product is a normal protein with a short half-life of only 15 min, while the p53 mutant proteins that form complexes with heat shock protein 70 in the cytoplasm and bind wild-type p53 have a longer half-life of several hours., Rearrangements resulting in loss of 17p (monosomy, deletion, unbalanced translocations involving 17p or isochromosome 17q), usually as part of a complex karyotypes have been observed in 5% of new cases of MDS... The p53 mutation is detected in about 5–20% of MDS de novo,,, ,, ,, , in 18% of patients with low-risk MDS and deletion 5q and in 25–70% in adult therapy-related MDS., ,, The p53 mutations are associated with complex karyotype with -5/5q-, short survival, increased risk to transformation to AML and poor response to therapy: patients with MDS de novo often present with excess of blasts, and patients with the 5q deletion have less response to lenalidomide... Although there is a general correlation between the expression of p53 protein and mutation, in some tumors with nonsense mutations in their genetic sequences (less than 20% of human tumors with p53 mutation), the protein expression cannot be detected... On the other hand, rare cases of positive p53 expression were not associated with the p53 mutation... Also, overexpression of this protein has been shown to be more common in patients in the refractory anemia with excess blasts subgroup... In 22 cases of secondary MDS studied in HCFMUSP, p53 immunoreactivity was observed in 33.3% and was associated in univariate analysis with poor survival (Figure 1)., The work published by Duarte et al. in this issue of the Revista Brasileira de Hematologia e Hemoterapia validates the value of p53 in bone marrow biopsies in low-risk MDS... Other studies have also shown its prognostic value in higher risk and secondary MDS... Due to the low cost of immunohistochemistry, reproducibility and availability in various centers of Brazil, we suggest the routine study of p53 expression in bone marrow biopsies of all MDS cases... The author declares no conflict of interest.

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Kaplan–Meier survival curve for secondary myeloid neoplasia according to immunoexpression of p53 in bone marrow biopsy.
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fig0005: Kaplan–Meier survival curve for secondary myeloid neoplasia according to immunoexpression of p53 in bone marrow biopsy.

Mentions: Kitagawa detected the expression of p53 by immunohistochemistry in 14% of patients with MDS, with half of them having progressed to AML.11 Also, overexpression of this protein has been shown to be more common in patients in the refractory anemia with excess blasts subgroup. In 22 cases of secondary MDS studied in HCFMUSP, p53 immunoreactivity was observed in 33.3% and was associated in univariate analysis with poor survival (Figure 1).24, 25


Scientific comment on tumor suppressor p53 protein expression: prognostic significance in patients with low-risk myelodysplastic syndrome.

Velloso ED - Rev Bras Hematol Hemoter (2014)

Kaplan–Meier survival curve for secondary myeloid neoplasia according to immunoexpression of p53 in bone marrow biopsy.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109737&req=5

fig0005: Kaplan–Meier survival curve for secondary myeloid neoplasia according to immunoexpression of p53 in bone marrow biopsy.
Mentions: Kitagawa detected the expression of p53 by immunohistochemistry in 14% of patients with MDS, with half of them having progressed to AML.11 Also, overexpression of this protein has been shown to be more common in patients in the refractory anemia with excess blasts subgroup. In 22 cases of secondary MDS studied in HCFMUSP, p53 immunoreactivity was observed in 33.3% and was associated in univariate analysis with poor survival (Figure 1).24, 25

View Article: PubMed Central - PubMed

Affiliation: Universidade de São Paulo (USP), São Paulo, SP, Brazil. Electronic address: elvira.velloso@yahoo.com.br.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic neoplasms, characterized by dysplastic findings with variable degree of bone marrow failure and proliferation of blast cells... Factors related to the individual (such as performance status, co-morbidities, age and nutritional status), biological (severity of cytopenias, transfusion need, cytogenetic abnormalities, percentage of blasts, bone marrow fibrosis, primary or secondary disease) and social (access to health care and medications) impact the survival... The models most commonly used in prognostic score for MDS de novo, such as the International Prognostic Scoring System (IPSS), the WHO Prognostic Scoring System (WPSS), and the Revised International Prognostic Scoring System (IPSS-R) basically use biological variables, obtained from the study of blood cell counts (cytopenias), percentage of blasts in bone marrow aspirate and cytogenetic findings., , Recently, cytogenetic findings were better defined and cytogenetic abnormalities were divided into 5 risk groups, noting that the higher the complexity observed in the karyotype, the worst the survival is., Even in patients with normal karyotype, many genetic mutations described by molecular biology techniques have been associated with prognosis... The p53 gene (located at 17p13) is a tumor suppressor gene of great importance for genetic stability and integrity of the genome... DNA damage of several types activates the 53 kDa nuclear phosphoprotein p53 protein, resulting in cell cycle arrest at the G1 (post-mitotic phase) and G2 (pre-mitotic) cell cycle checkpoints necessary for DNA repair... The inactivation of the p53 gene in both alleles, loss of heterozygous (LOH), by mutations or deletions have been related to the predisposition to neoplastic transformation... The wild type gene product is a normal protein with a short half-life of only 15 min, while the p53 mutant proteins that form complexes with heat shock protein 70 in the cytoplasm and bind wild-type p53 have a longer half-life of several hours., Rearrangements resulting in loss of 17p (monosomy, deletion, unbalanced translocations involving 17p or isochromosome 17q), usually as part of a complex karyotypes have been observed in 5% of new cases of MDS... The p53 mutation is detected in about 5–20% of MDS de novo,,, ,, ,, , in 18% of patients with low-risk MDS and deletion 5q and in 25–70% in adult therapy-related MDS., ,, The p53 mutations are associated with complex karyotype with -5/5q-, short survival, increased risk to transformation to AML and poor response to therapy: patients with MDS de novo often present with excess of blasts, and patients with the 5q deletion have less response to lenalidomide... Although there is a general correlation between the expression of p53 protein and mutation, in some tumors with nonsense mutations in their genetic sequences (less than 20% of human tumors with p53 mutation), the protein expression cannot be detected... On the other hand, rare cases of positive p53 expression were not associated with the p53 mutation... Also, overexpression of this protein has been shown to be more common in patients in the refractory anemia with excess blasts subgroup... In 22 cases of secondary MDS studied in HCFMUSP, p53 immunoreactivity was observed in 33.3% and was associated in univariate analysis with poor survival (Figure 1)., The work published by Duarte et al. in this issue of the Revista Brasileira de Hematologia e Hemoterapia validates the value of p53 in bone marrow biopsies in low-risk MDS... Other studies have also shown its prognostic value in higher risk and secondary MDS... Due to the low cost of immunohistochemistry, reproducibility and availability in various centers of Brazil, we suggest the routine study of p53 expression in bone marrow biopsies of all MDS cases... The author declares no conflict of interest.

No MeSH data available.


Related in: MedlinePlus