Significance of p53 overexpression in bone marrow biopsies from patients with bone marrow failure: aplastic anemia, hypocellular refractory anemia, and hypercellular refractory anemia

Elghetany, M. Tarek; Vyas, Sanjiv H.; Yuoh, Gbo

doi:10.1007/s002770050455

Cited by 29 publications

(25 citation statements)

References 19 publications

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“…58 Clearly, similar to the pathological role of p53 in bone marrow developmental defects, 59 p53, when abnormally active, also serves as a pathogenic agent in Down syndrome development.…”

Section: Role Of the P53-mir-1246-dyrk1a-nfat Pathway In Down Syndromementioning

confidence: 99%

MiR-1246: A new link of the p53 family with cancer and Down syndrome

et al. 2012

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“…58 Clearly, similar to the pathological role of p53 in bone marrow developmental defects, 59 p53, when abnormally active, also serves as a pathogenic agent in Down syndrome development.…”

Section: Role Of the P53-mir-1246-dyrk1a-nfat Pathway In Down Syndromementioning

confidence: 99%

MiR-1246: A new link of the p53 family with cancer and Down syndrome

et al. 2012

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“…Myelodysplastic syndrome is characterized by dysplastic and ineffective normocellular or hypercellular bone marrow with variable degree of peripheral blood cytopenia along with higher risk of transformation to acute myeloid leukemia (AML). However, 8-46% patients of MDS have hypoplastic bone marrow [2]. In this situation, it is often very diffi cult to determine whether the patient has AA or hypoplastic MDS (HMDS).…”

Section: Introductionmentioning

confidence: 99%

“…Various attempts have been made in the past to differentiate these entities using morphological, histological and conventional cytogenetics [1][2][3][4][5][6][7][8][9][10][11]. In addition, differences in the pattern of proliferation of bone marrow cells in AA and MDS have been reported [2,[12][13] through immunohistochemistry techniques using several antigens (p53, proliferating cell nuclear antigen i.e.…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic and prognostic values of S-phase fraction and aneuploidy in patients with bone marrow aplasia

Tripathi

Tripathi²,

Kumar³

et al. 2009

Indian J Hematol Blood Transfus

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Aim It is often diffi cult and challenging task to differentiate aplastic anemia (AA) from hypoplastic myelodysplastic syndrome (HMDS) among the patients with bone marrow aplasia. This is possibly because of the considerable clinical, cytological and histological similarities between these two disorders. As prognostic and therapeutic approach to AA and HMDS are different, it is imperative to differentiate them at the time of initial diagnosis. Various attempts have been made in the past to differentiate AA from HMDS. In the present study, we explored the value of certain new parameters i.e. S-phase fraction (SPF) and aneuploidy that could be used for this purpose. Materials and methodsThe study included 46 consecutive patients with aplastic anemia, 15 patients with HMDS along with 32 age and sex-matched control subjects. Sphase fraction and aneuploidy analysis was carried out by fl ow cytometry using Mod Fit-LT V3.0 software. ResultsThe mean SPF value was signifi cantly lower (p=0.02) in patients with AA and higher (p=0.01) in HMDS as compared to that of the control. Aneuploidy was present in 15.2% patients with AA and in 33.3% HMDS cases. During follow-up, 4 patients with AA developed MDS, out of these, three patients had aneuploidy as well as high SPF value at the time of diagnosis. Two patients with HMDS who had aneuploidy and high SPF, converted into AML. Eleven patients died during the study, in whom 8 had aneuploidy and high SPF value. ConclusionWe conclude that high SPF value and presence of aneuploidy favour the diagnosis of HMDS rather than AA. SPF and aneuploidy may be important parameters in patients with AA to predict their propensity to evolve into myelodysplastic syndrome and acute myeloid leukemia. SPF value may also be useful in the early diagnosis of HMDS before morphologically evidence of dysplasia is apparent.

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“…These diagnostic challenges underline the role of bone marrow histology with a panel of immunohistochemical markers in the work-up of unclear cytopenias with/without dysplasia. Immunohistochemical staining for p53 may provide additional information to help differentiate hypoplastic MDS from AA [23,24]. Strong nuclear p53 staining has in previous studies been shown to be useful as both a diagnostic and a prognostic marker [25,26], and may be associated with an underlying TP53 mutation [27].…”

Section: Cytopenia With Clonal Haematopoiesis Not Fulfilling Mds Critmentioning

confidence: 99%

Challenges in Diagnosing Myelodysplastic Syndromes in the Era of Genetic Testing: Proceedings of the 13th Workshop of the European Bone Marrow Working Group

et al. 2018

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The 13th workshop of the European Bone Marrow Working Group in Utrecht, The Netherlands, was devoted to studying myelodysplastic syndromes (MDS) and their boundaries. The panel received 44 cases submitted to the 3 invited categories, which included: reactive cytopenias with dysplasia, idiopathic cytopenia of undetermined significance, clonal haematopoiesis of indeterminate potential, idiopathic dysplasia of uncertain significance and overt MDS. For this summary, we have selected 17 cases that highlight difficulties in separating true MDS from other causes of cytopenia and the intricate relationship between clonal haematopoiesis and true MDS. In addition, cases of overt MDS with challenging features were also selected. All cases were stained for p53 expression. Using instructive submitted cases we discuss the following: (1) cytopenia with clonal haematopoiesis not fulfilling MDS criteria, (2) cytopenia and/or dysplasia with germline mutations and/or familial history suggesting an underlying gene defect, (3) MDS based on a recurrent chromosomal abnormality and (4) overt MDS with diagnostic difficulties due to concurrent treatment or disease. The lively discussion in the open forum of the workshop illustrated the need for better integrative understanding of the evolution of acquired genetic abnormalities in haematopoiesis, and the challenge of diagnosing true MDS in cytopenic patients with genetic abnormalities, either germline or acquired.

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Significance of p53 overexpression in bone marrow biopsies from patients with bone marrow failure: aplastic anemia, hypocellular refractory anemia, and hypercellular refractory anemia

Cited by 29 publications

References 19 publications

MiR-1246: A new link of the p53 family with cancer and Down syndrome

MiR-1246: A new link of the p53 family with cancer and Down syndrome

Diagnostic and prognostic values of S-phase fraction and aneuploidy in patients with bone marrow aplasia

Challenges in Diagnosing Myelodysplastic Syndromes in the Era of Genetic Testing: Proceedings of the 13th Workshop of the European Bone Marrow Working Group

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