International prognostic scoring system and <i>TP53</i> mutations are independent prognostic indicators for patients with myelodysplastic syndrome

Kita-Sasai, Yuri; Horiike, Shigeo; Misawa, Shinichi; Kaneko, Hiroto; Kobayashi, Miyako; Nakao, Mitsushige; Nakagawa, Hitoshi; Fujii, Hiroshi

doi:10.1046/j.1365-2141.2001.03073.x

Cited by 85 publications

(48 citation statements)

References 13 publications

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“…TP53 mutations in 9Á4% of MDS patients in our large single institution study is slightly higher than in previous reports (Jonveaux et al, 1991;Ludwig et al, 1992;Lai et al, 1995), although some reports have shown frequencies around 11-14% (Wattel et al, 1994;Kaneko et al, 1995;Kita-Sasai et al, 2001). The overall higher incidence in our study is possibly due to the sensitive technique, which detected low level clones (<20% mutant allele burden in 8 patients), the inclusion of patients with therapy-related myeloid neoplasms and also sequencing of the whole gene.…”

Section: Discussioncontrasting

confidence: 51%

TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis

et al. 2013

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SummaryThis study aimed to determine the incidence/prognostic impact of TP53 mutation in 318 myelodysplastic syndrome (MDS) patients, and to correlate the changes to cytogenetics, single nucleotide polymorphism array karyotyping and clinical outcome. The median age was 65 years (17-89 years) and median follow-up was 45 months [95% confidence interval (CI) 27-62 months]. TP53 mutations occurred in 30 (9Á4%) patients, exclusively in isolated del5q (19%) and complex karyotype (CK) with -5/5q-(72%), correlated with International Prognostic Scoring System intermediate-2/high, TP53 protein expression, higher blast count and leukaemic progression. Patients with mutant TP53 had a paucity of mutations in other genes implicated in myeloid malignancies. Median overall survival of patients with TP53 mutation was shorter than wild-type (9 versus 66 months, P < 0Á001) and it retained significance in multivariable model (Hazard Ratio 3Á8, 95% CI 2Á3-6Á3,P < 0Á001). None of the sequentially analysed samples showed a disappearance of the mutant clone or emergence of new clones, suggesting an early occurrence of TP53 mutations. A reduction in mutant clone correlated with response to 5-azacitidine, however clones increased in nonresponders and persisted at relapse. The adverse impact of TP53 persists after adjustment for cytogenetic risk and is of practical importance in evaluating prognosis. The relatively common occurrence of these mutations in two different prognostic spectrums of MDS, i.e. isolated 5q-and CK with -5/5q-, possibly implies two different mechanistic roles for TP53 protein.

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Section: Discussioncontrasting

confidence: 51%

TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis

et al. 2013

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“…TP53 mutations are exceedingly rare in the 5q-syndrome, 13 however, they frequently occur in MDS with complex karyotypes including del(5q) or in therapyrelated MDS, invariably implying a poor outcome, 14,15 The frequency of small fractions of BM progenitors with abnormal p53 expression, which may fall below the detection threshold for a mutational analysis, is unknown in MDS with isolated del(5q).…”

Section: Mutated Tp53 Pre-treatmentmentioning

confidence: 99%

Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression

Jädersten¹,

Saft²,

Pellagatti³

et al. 2009

Haematologica

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IntroductionThe immunomodulatory drug lenalidomide is a potent treatment for low-risk myelodysplastic syndrome (MDS) with a karyotype including the deletion of 5q31 (del[5q]), with 67% achieving transfusion independency, and 45% obtaining complete cytogenetic remission.1 However, 50% of responders relapse within two years, and the estimated risk of leukemic transformation at ten years is 15% for cytogenetic responders and 67% for patients without a cytogenetic response. Design and Methods Patients and treatment Bone marrow assessment and immunohistochemistryHistopathology and morphology were assessed on consecutive bone marrow (BM) samples. Immunohistochemistry on paraffin-embedded sections was performed using mouse monoclonal antibodies: p53 (clone DO-1; Santa Cruz Biotechnology, Santa Cruz, CA, USA); CD34 (DakoCytomation, Glostrup, Denmark). Ten normal BMs were stained and demonstrated p53 expression in less than 0.01% of cells. Acknowledgments: we express our warmest gratitude for excellent technical support to Lalla Forsblom (cell separation and culture) and Monika Jansson (FISH analysis) at

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“…5,6 In particular, TP53 mutations have been shown to confer resistance to lenalidomide in MDS with del(5q).…”

mentioning

confidence: 99%

Response to azacitidine is independent of p53 expression in higher-risk myelodysplastic syndromes and secondary acute myeloid leukemia

et al. 2014

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International prognostic scoring system and TP53 mutations are independent prognostic indicators for patients with myelodysplastic syndrome

Cited by 85 publications

References 13 publications

TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis

TP53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis

Clonal heterogeneity in the 5q- syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression

Response to azacitidine is independent of p53 expression in higher-risk myelodysplastic syndromes and secondary acute myeloid leukemia

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