Bone marrow fibrosis at diagnosis is associated with <scp>TP</scp>53 overexpression and adverse prognosis in low‐risk myelodysplastic syndrome

Duarte, Fernando Barroso; Barbosa, Maritza Cavalcante; Santos, Talyta Ellen de Jesus dos; Lemes, Romélia Pinheiro Gonçalves; Vasconcelos, João Paulo; Vasconcelos, Paulo Roberto Leitão de; Rocha, Francisco Dário; Zalcberg, Ilana; Coutinho, Diego F.

doi:10.1111/bjh.14656

Cited by 10 publications

(6 citation statements)

References 9 publications

(15 reference statements)

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“…In fact, the degree of BM fibrosis was related to parameters of erythropoietic failure, marrow cellularity, p53 protein accumulation, WT1 gene expression, and serum levels of CXCL9 and CXCL10 [87]. The correlation between BM fibrosis and p53 overexpression supports the hypothesis that patients with BM fibrosis at diagnosis can have a worse clinical outcome [88,89]. In view of these considerations, because sequencing technologies are not always available for TP53 mutational status characterization, p53 ICH should be considered a feasible alternative to TP53 sequencing [76].…”

Section: P53 Protein Expressionmentioning

confidence: 61%

TP53 in Myelodysplastic Syndromes: Recent Biological and Clinical Findings

Cumbo

Tota

Anelli

et al. 2020

IJMS

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TP53 dysregulation plays a pivotal role in the molecular pathogenesis of myelodysplastic syndromes (MDS), identifying a subgroup of patients with peculiar features. In this review we report the recent biological and clinical findings of TP53-mutated MDS, focusing on the molecular pathways activation and on its impact on the cellular physiology. In MDS, TP53 mutational status is deeply associated with del(5q) syndrome and its dysregulation impacts on cell cycle, DNA repair and apoptosis inducing chromosomal instability and the clonal evolution of disease. TP53 defects influence adversely the MDS clinical outcome and the treatment response rate, thus new therapeutic approaches are being developed for these patients. TP53 allelic state characterization and the mutational burden evaluation can therefore predict prognosis and identify the subgroup of patients eligible for targeted therapy. For these reasons, in the era of precision medicine, the MDS diagnostic workup cannot do without the complete assessment of TP53 mutational profile.

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Section: P53 Protein Expressionmentioning

confidence: 61%

TP53 in Myelodysplastic Syndromes: Recent Biological and Clinical Findings

Cumbo

Tota

Anelli

et al. 2020

IJMS

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“…An Asian study demonstrated that SRSF2 mutation is closely associated with male sex and older age, and the prognostic impact of SRSF2 mutation might be attributed to its close association with old age [80]. TP53 mutations in MDS are strongly correlated with childhood and therapy-related MDS [87,111,112]. U2AF1 mutation is more prevalent in younger MDS patients [86], and the U2AF1 mutation is strongly associated with isolated trisomy 8 and del(20q) in Asian people, but not in Caucasian people, and is characterized by a younger age of MDS onset (median 39 year-old) [113].…”

Section: Molecular Geneticsmentioning

confidence: 99%

Asian Population Is More Prone to Develop High-Risk Myelodysplastic Syndrome, Concordantly with Their Propensity to Exhibit High-Risk Cytogenetic Aberrations

Jiang

Eveillard

Couturier

et al. 2021

Cancers

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This study explores the hypothesis that genetic differences related to an ethnic factor may underlie differences in phenotypic expression of myelodysplastic syndrome (MDS). First, to identify clear ethnic differences, we systematically compared the epidemiology, and the clinical, biological and genetic characteristics of MDS between Asian and Western countries over the last 20 years. Asian MDS cases show a 2- to 4-fold lower incidence and a 10-year younger age of onset compared to the Western cases. A higher proportion of Western MDS patients fall into the very low- and low-risk categories while the intermediate, high and very high-risk groups are more represented in Asian MDS patients according to the Revised International Prognostic Scoring System. Next, we investigated whether differences in prognostic risk scores could find their origin in differential cytogenetic profiles. We found that 5q deletion (del(5q)) aberrations and mutations in TET2, SF3B1, SRSF2 and IDH1/2 are more frequently reported in Western MDS patients while trisomy 8, del(20q), U2AF1 and ETV6 mutations are more frequent in Asian MDS patients. Treatment approaches differ between Western and Asian countries owing to the above discrepancies, but the overall survival rate within each prognostic group is similar for Western and Asian MDS patients. Altogether, our study highlights greater risk MDS in Asians supported by their cytogenetic profile.

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“…There is growing interest in the detrimental role of increased bone marrow fibrosis (BMF) in several hematologic conditions, including bone marrow failure and myelodysplastic syndromes as well as acute and chronic myeloid leukemia, chronic lymphocytic leukemia, and multiple myeloma. 1,2 No systematic studies on bone marrow features have been conducted in autoimmune hemolytic anemia (AIHA), where bone marrow compensatory response, usually evaluated with reticulocyte counts, is known to be one of the main mechanisms of the disease and has been shown to impact on its severity. 3 Here we evaluated for the first time bone marrow histology in 47 primary AIHA patients, classified as cold agglutinin disease (CAD, DAT-positive for C), warm (WAIHA, DATpositive for IgG or IgG 1 C), mixed (DAT-positive for IgG 1 C and high titer cold agglutinins), and atypical cases (DAT-negative, IgA-positive, warm IgM).…”

Section: Prognostic Impact Of Bone Marrow Fibrosis and Dyserythropoiementioning

confidence: 99%

Prognostic impact of bone marrow fibrosis and dyserythropoiesis in autoimmune hemolytic anemia

et al. 2018

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Bone marrow fibrosis at diagnosis is associated with TP53 overexpression and adverse prognosis in low‐risk myelodysplastic syndrome

Cited by 10 publications

References 9 publications

TP53 in Myelodysplastic Syndromes: Recent Biological and Clinical Findings

TP53 in Myelodysplastic Syndromes: Recent Biological and Clinical Findings

Asian Population Is More Prone to Develop High-Risk Myelodysplastic Syndrome, Concordantly with Their Propensity to Exhibit High-Risk Cytogenetic Aberrations

Prognostic impact of bone marrow fibrosis and dyserythropoiesis in autoimmune hemolytic anemia

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