Diagnostic significance of dysplastic features of peripheral blood polymorphs in myelodysplastic syndromes

Hast, Robert; Nilsson, Ingmar; Widell, Susanne; Öst, Åke

doi:10.1016/0145-2126(89)90142-2

Cited by 41 publications

(34 citation statements)

References 5 publications

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“…Finally, the AME-infected cells demonstrated evidence of dysplastic features in the granulocytic lineage consisting of cytoplasmic hypogranulation and a relatively higher percentage of cells with ring-shaped nuclei compared to the corresponding stage of granulocytic di erentiation in both the control cells and the AME-C cells (Figure 9). Both these features were described as characteristics of MDS cells (Langenhuijsen, 1984;Hast et al, 1989). In contrast, the AME-C and the empty vector cells showed normal cytoplasmic granulation and nuclear segmentation patterns ( Figure 9), suggesting that CtBP1 is required and su cient for abnormal di erentiation of murine hematopoietic precursors.…”

Section: Ame Requires Ctbp1-binding For Immortalization Of Normal Murmentioning

confidence: 99%

The leukemia-associated transcription repressor AML1/MDS1/EVI1 requires CtBP to induce abnormal growth and differentiation of murine hematopoietic cells

et al. 2002

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The leukemia-associated fusion gene AML1/MDS1/ EVI1 (AME) encodes a chimeric transcription factor that results from the (3;21)(q26;q22) translocation. This translocation is observed in patients with therapy-related myelodysplastic syndrome (MDS), with chronic myelogenous leukemia during the blast crisis (CML-BC), and with de novo or therapy-related acute myeloid leukemia (AML). AME is obtained by in-frame fusion of the AML1 and MDS1/EVI1 genes. We have previously shown that AME is a transcriptional repressor that induces leukemia in mice. In order to elucidate the role of AME in leukemic transformation, we investigated the interaction of AME with the transcription co-regulator CtBP1 and with members of the histone deacetylase (HDAC) family. In this report, we show that AME physically interacts in vivo with CtBP1 and HDAC1 and that these co-repressors require distinct regions of AME for interaction. By using reporter gene assays, we demonstrate that AME represses gene transcription by CtBP1-dependent and CtBP1-independent mechanisms. Finally, we show that the interaction between AME and CtBP1 is biologically important and is necessary for growth upregulation and abnormal di erentiation of the murine hematopoietic precursor cell line 32Dc13 and of murine bone marrow progenitors.

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Section: Ame Requires Ctbp1-binding For Immortalization Of Normal Murmentioning

confidence: 99%

The leukemia-associated transcription repressor AML1/MDS1/EVI1 requires CtBP to induce abnormal growth and differentiation of murine hematopoietic cells

et al. 2002

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“…These cases of AML defined as AML with trilineage myelodysplasia (AML/TLMD) have been reported, accounting for 10-15% of de novo AML [3,6,7,10]. Furthermore, in patients with AML/TLMD who achieved CR, relapse occurred much more earlier than in patients without dysplastic features [8,9,13]. The lack of prospective studies is one of the important reasons why the prognostic relevance of TLMD detection remains unclear.…”

Section: Introductionmentioning

confidence: 97%

Prognostic significance of dysplastic features of hematopoiesis in patients with de novo acute myelogenous leukemia

Kahl

Florschütz

Müller

et al. 1997

Annals of Hematology

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The detection of dysplastic features of hematopoiesis in de novo acute myeloid leukemia (AML) by light microscopy is defined as AML with trilineage myelodysplasia (AML/TLMD). The prognostic relevance of these dysplastic features for patients with de novo AML remains unclear. In order to evaluate the role of dysplasia in de novo AML, bone marrow aspirates from 69 patients were analyzed prospectively and investigated separately for erythropoiesis, granulopoiesis and megakaryopoiesis by three independent investigators. The overall complete remission (CR) rate was 48.8% and partial remission (PR) or nonresponders constituted 52.2% of the patients investigated. The median overall survival time was 5 months with a disease-free interval of 3.5 months for all patients. Dysgranulopoiesis (DysG) was observed in 30.4%, dysmegakaryopoiesis (DysM) in 50.7%, and dyserythropoiesis (DysE) in 43.5%. Of all patients, 26.0% showed trilineage dysplastic features and were thus classified as AML/TLMD. A significantly worse prognosis (Kaplan-Meyer plot, Student's t-test) was calculated for those patients with detection of only DysG (p = 0.002), DysM (p = 0.02), DysE (p = 0.04) as compared with patients without any dysplastic signs. An unfavorable karyotype was correlated with patients showing DysG (P = 0.02) and DysM (P = 0.04). For these patients with an unfavorable karyotype, the occurrence of any dysplastic features had no additional prognostic impact. Dysplastic features (DysG, DysM, DysE) seem to be an important prognostic factor in de novo AML correlating with short overall survival. DysG and DysM correlated well with the appearance of unfavorable chromosomal abnormalities. It may be reasonable to assume that patients with dysplastic features should be considered for more aggressive treatment schedules at the time of diagnosis.

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“…It could be speculated that monolobar and clumped hyposegmented neutrophils signify an intensified form of abnormal nuclear lobulation above the bi-lobed form, which might explain their prognostic impact. 17 …”

Section: Multivariate Analysesmentioning

confidence: 99%

A new disease categorization of low-grade myelodysplastic syndromes based on the expression of cytopenia and dysplasia in one versus more than one lineage improves on the WHO classification

et al. 2007

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Multilineage dysplasia was advanced by the World Health Organization to increase prognostic accuracy in myelodysplastic syndromes (MDS) classification. We performed a structured cytomorphological examination of bone marrow (BM) in 221 low-grade MDS patients, this in conjunction with strict guidelines for cytopenias. A dysplasia scoring system was developed utilizing dysplastic changes, which were associated with worse outcome on univariate and multivariate analysis corrected for the International Prognostic Scoring System (IPSS). Dysplasia X10% in one BM lineage and one cytopenia constituted the low-risk category UCUD or Unilineage Cytopenia and Unilineage Dysplasia. The high-risk category comprised patients with cytopenia in X2 lineages and dysplasia in X2 BM lineages, namely MCMD or Multilineage Cytopenia and Multilineage Dysplasia. Intermediate-risk patients had one cytopenia and multilineage dysplasia, or cytopenia in X2 lineages and unilineage BM dysplasia, designated UCMD/MCUD or Unilineage Cytopenia and Multilineage Dysplasia/Multilineage Cytopenia and Unilineage Dysplasia. This system utilizing cytopenia-dysplasia scoring at diagnosis enabled comprehensive categorization of low-grade MDS cases that predicted for overall as well as leukemia-free survival. Cytopenia-dysplasia categorization added additional prognostic values to the lower risk IPSS categories. This suggests that a standardized dysplasia scoring system, used in conjunction with cytopenia, could improve diagnostic and prognostic sub-categorization of MDS patients.

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Diagnostic significance of dysplastic features of peripheral blood polymorphs in myelodysplastic syndromes

Cited by 41 publications

References 5 publications

The leukemia-associated transcription repressor AML1/MDS1/EVI1 requires CtBP to induce abnormal growth and differentiation of murine hematopoietic cells

The leukemia-associated transcription repressor AML1/MDS1/EVI1 requires CtBP to induce abnormal growth and differentiation of murine hematopoietic cells

Prognostic significance of dysplastic features of hematopoiesis in patients with de novo acute myelogenous leukemia

A new disease categorization of low-grade myelodysplastic syndromes based on the expression of cytopenia and dysplasia in one versus more than one lineage improves on the WHO classification

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