scholarly journals High expression of myocyte enhancer factor 2C predicts poor prognosis for adult acute myeloid leukaemia with normal karyotype

2020 ◽  
Vol 189 (1) ◽  
Author(s):  
Xiaoyu Xu ◽  
Zhao Zeng ◽  
Li Huo ◽  
Hong Liu ◽  
Yan Yu ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Poor Prognosis ◽  
Normal Karyotype ◽  
High Expression ◽  
Myocyte Enhancer Factor ◽  
Acute Myeloid ◽  
Enhancer Factor

scholarly journals Detailed molecular characterisation of acute myeloid leukaemia with a normal karyotype using targeted DNA capture

Leukemia ◽  
2013 ◽  
Vol 27 (9) ◽  
pp. 1820-1825 ◽  
Author(s):  
N Conte ◽  
I Varela ◽  
C Grove ◽  
N Manes ◽  
K Yusa ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Normal Karyotype ◽  
Molecular Characterisation ◽  
Dna Capture ◽  
Acute Myeloid

Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia

2014 ◽  
Vol 94 (5) ◽  
pp. 419-423 ◽  
Author(s):  
Vladimir Lazarevic ◽  
Ann-Sofi Hörstedt ◽  
Bertil Johansson ◽  
Petar Antunovic ◽  
Rolf Billström ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Poor Prognosis ◽  
Population Based ◽  
Acute Myeloid

Feasibility ofBAALCgene expression for detection of minimal residual disease and risk stratification in normal karyotype acute myeloid leukaemia

2016 ◽  
Vol 175 (5) ◽  
pp. 904-916 ◽  
Author(s):  
Simone Weber ◽  
Torsten Haferlach ◽  
Tamara Alpermann ◽  
Karolína Perglerová ◽  
Susanne Schnittger ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Normal Karyotype ◽  
Minimal Residual ◽  
Acute Myeloid

scholarly journals Acute myeloid leukaemia expressing the leucocyte integrin CD11b - a new leukaemic syndrome with poor prognosis: result of an ECOG database analysis

1998 ◽  
Vol 100 (2) ◽  
pp. 265-272 ◽  
Author(s):  
Elisabeth Paietta ◽  
Janet Andersen ◽  
Jorge Yunis ◽  
Jacob M. Rowe ◽  
Peter A. Cassileth ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Poor Prognosis ◽  
Database Analysis ◽  
Acute Myeloid

Development of a Human Acute Myeloid Leukaemia Screening Panel and Identification of Novel Gene Mutations.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2991-2991
Author(s):  
Jude Fitzgibbon ◽  
Matthew Smith ◽  
Rachael Arch ◽  
Lan-Lan Smith ◽  
Nigel Bainton ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Candidate Genes ◽  
Gene Mutations ◽  
Normal Karyotype ◽  
Risk Groups ◽  
Cyclin D3 ◽  
Kit Mutation ◽  
Individual Gene ◽  
Acute Myeloid

Abstract Mutation studies in Acute Myeloid Leukaemia (AML) are complicated by the existence of distinct morphological and cytogenetic subtypes; consequently although mutations in any one gene may occur in only 5% of AML, the frequency of mutation may differ both between the different FAB-types and cytogenetic risk groups studied. It is important therefore not only to validate the screening methodology used but also the suitability of the patient panel tested. A screening panel was developed allowing detection of novel recurring gene mutations within samples derived from patients with AML. Mutation analysis of 6 previously described genes (RUNX1, FLT3, KIT, CEBPA, PTPN11, NRAS) and 2 candidate genes (CCND3, FES) were carried out in a cohort of 175 AML samples representing all FAB types (except M3) and cytogenetic risk groups using a combination of SSCP, DHPLC and sequence analysis. One hundred and fifteen mutations were identified in 97 (55%) patients comprising 81 patients (46%) with one mutation, 14 patients (8%) with 2 mutations, and 2 patients (1%) with 3 mutations. Fifty-five out of 88 (63%) patients with normal karyotype AML had at least one mutation. There was was a weak negative association between FLT3 ITD and loop mutation (p = 0.095), a positive association between KIT mutation and favourable risk cytogenetics (p = 0.001), CEBPA mutation and intermediate risk/normal cytogenetics (p = 0.045) and PTPN11 mutation and poor risk disease (p = 0.001). The frequency of individual gene mutation was in accordance with previously published studies. Three novel mutations of FLT3 (Y589D, D839G, Y842H) were detected in 4 patients that would have been overlooked by conventional gel electrophoresis techniques. A single in frame 51bp deletion of nucleotide 939 – 990, resulting in a deletion of 17 amino acids at the carboxyl-terminus of the cyclin D3 protein was identified in a single patient. Overall, both the pattern and mutation frequencies reported in this cohort are similar to those in the literature supporting its further use as an investigational tool in the evaluation of candidate genes in the genesis of myeloid malignancy.

Multiplex Quantum Dot ISH Measurement of Gene Expression in Tissue Microarrays Identifies HOXA9 and DNMT3A as Markers of Poor Response to Chemotherapy in Patients with Acute Myeloid Leukaemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2530-2530
Author(s):  
Eleni Tholouli ◽  
Sara A MacDermott ◽  
Judith A Hoyland ◽  
Caroline Glennie ◽  
Ric Swindell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multivariate Analysis ◽  
Quantum Dot ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Poor Response ◽  
Tissue Microarrays ◽  
High Expression ◽  
Response To Chemotherapy ◽  
Acute Myeloid

Abstract Microarray-based expression profiling has identified prognostic gene signatures for many cancers and validation is required in clinical samples. However, most clinical material is in the form of formalin fixed and paraffin embedded tissue (FFPET) in which gene expression analysis is problematic. We have developed a generic quantum dot (QD) based multiplexed in-situ hybridization (ISH) method enabling quantitative localization of multiple mRNA targets in FFPET. We expand on our previous work introducing a method for standardization of ISH signal, enabling comparative measurement of gene expression across multiple samples. This was applied to tissue microarrays (TMAs) using archived trephine biopsies from patients with acute myeloid leukaemia (AML) to identify prognostic genes. A total of 15 TMAs were prepared using FFPET samples from 240 patients with AML diagnosed and treated between 1994 and 2005 at Manchester Royal Infirmary (Manchester, UK). For the analysis, 192 patients were included as the remainder either died before, during or immediately after one course of chemotherapy or there was incomplete data collection. The median age was 52 years (range 17–77) and all patients received intensive chemotherapy according to standard UK MRC AML protocols. Three cores were taken from each sample for TMA preparation. A standard was prepared using a cell pellet obtained from whole blood white cells which was embedded, in triplicate, in each TMA. QD-ISH was performed for nine genes recognized to be of prognostic value in AML. Triplex QD-ISH using QD labeled anti-sense cDNA oligonucleotides was performed for the following targets: Bcl2, survivin and XIAP; DNMT1, DNMT3A and DNMT3B; HOXA4, HOXA9 and Meis1. Signal intensity for each gene was measured using spectral imaging. Scrambled sense cDNA oligonucleotides were used to measure the level of background staining for each gene in each core. Background noise was corrected for by dividing expression levels of anti-sense probes by that of the scrambled probe, for both samples and standards. This enabled direct comparison between TMAs as gene expression values of samples were normalized against the standard. The mean expression of each gene was calculated for each patient, divided into quartiles and correlated with clinical outcome data. Statistical analysis was performed using contingency tables, the chi-square test and Mann Whitney-U. Overall survival (OS) and disease free survival (DFS) were displayed using the Kaplan-Meier method and Cox regression was performed for univariate and multivariate analysis. The OS in this cohort of patients was 43% at 5 years with 80% achieving complete remission (CR) after induction chemotherapy. Patient age (<60 years), WCC (<100×109/l) at diagnosis, cytogenetics (good and intermediate risk) and low HOXA4 expression (median 577 [95%CI 325–828]) were all associated with improved OS (p<0.0001; p=0.02; p<0.0001; p=0.013) and DFS (p<0.0001; p=0.013; p<0.0001; p=0.025) on univariate and multivariate analysis. High expression of HOXA9 (median 0.843 [0.145–7.479]; p<0.0001) and DNMT3A (median 1.305 [0.073–5.477]; p=0.04) were associated with failure to achieve CR. High Meis1 expression was found to be of borderline significance for poor response to chemotherapy (median 0.716 [0.051–7.840]; p=0.05). Expression levels of the remaining 5 genes did not show any correlation with CR, DFS or OS. These findings are consistent with recently published data regarding the prognostic significance of various new markers. In line with others we have demonstrated low expression of HOXA4 is an independent good prognostic marker in adult AML. Although high expression of HOXA9, DNMT3A and Meis1 was associated with inferior CR rates in our study, OS and DFS were not adversely affected. This may be related to improvements and more aggressive clinical practice (eg stem cell transplantation) over recent years which can overcome potential deleterious gene effects. These results demonstrate that the application of a standardized, quantitative multiplex QD-ISH can be used for identification of prognostic markers in FFPET samples. The advantages of this method include its application to TMAs which allows high sample throughput, use of archived materials and its transferability across a spectrum of malignancies.

scholarly journals The expression of co-stimulatory molecules and their relation- ship to the prognosis of human acute myeloid leukaemia: poor prognosis of B7-2-positive leukaemia

1998 ◽  
Vol 102 (5) ◽  
pp. 1257-1262 ◽  
Author(s):  
Akinori Maeda ◽  
Kokichi Yamamoto ◽  
Kouhei Yamashita ◽  
Kohsuke Asagoe ◽  
Masaharu Nohgawa ◽  
...  
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Poor Prognosis ◽  
Acute Myeloid
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