scholarly journals Outcome after allogeneic transplantation for adult acute myeloid leukemia patients exhibiting isolated or associated trisomy 8 chromosomal abnormality: a survey on behalf of the ALWP of the EBMT

2009 ◽  
Vol 44 (9) ◽  
pp. 589-594 ◽  
Author(s):  
P Chevallier ◽  
◽  
M Labopin ◽  
A Nagler ◽  
P Ljungman ◽  
...  
2013 ◽  
Vol 31 (1) ◽  
pp. 95-103 ◽  
Author(s):  
Stefan Gröschel ◽  
Richard F. Schlenk ◽  
Jan Engelmann ◽  
Veronika Rockova ◽  
Veronica Teleanu ◽  
...  

Purpose To evaluate the prognostic value of ecotropic viral integration 1 gene (EVI1) overexpression in acute myeloid leukemia (AML) with MLL gene rearrangements. Patients and Methods We identified 286 patients with AML with t(11q23) enrolled onto German-Austrian Acute Myeloid Leukemia Study Group and Dutch-Belgian-Swiss Hemato-Oncology Cooperative Group prospective treatment trials. Material was available from 177 AML patients for EVI1 expression analysis. Results We divided 286 MLL-rearranged AMLs into three subgroups: t(9;11)(p22;q23) (44.8%), t(6;11)(q27;q23) (14.7%), and t(v;11q23) (40.5%). EVI1 overexpression (EVI1+) was found in 45.8% of all patients with t(11q23), with t(6;11) showing the highest frequency (83.9%), followed by t(9;11) at 40.0%, and t(v;11q23) at 34.8%. Concurrent gene mutations were rare or absent in all three subgroups. Within all t(11q23) AMLs, EVI1+ was the sole prognostic factor, predicting for inferior overall survival (OS; hazard ratio [HR], 2.06; P = .003), relapse-free survival (HR, 2.28; P = .002), and event-free survival (HR, 1.79; P = .009). EVI1+ AMLs with t(11q23) in first complete remission (CR) had a significantly better outcome after allogeneic transplantation compared with other consolidation therapies (5-year OS, 54.7% v 0%; Mantel-Byar, P = .0006). EVI1− t(9;11) AMLs had lower WBC counts, more commonly FAB M5 morphology, and frequently had additional trisomy 8 (39.6%; P < .001). Among t(9;11) AMLs, EVI1+ again was the sole independent adverse prognostic factor for survival. Conclusion Deregulated EVI1 expression defines poor prognostic subsets among AML with t(11q23) and AML with t(9;11)(p22;q23). Patients with EVI1+ MLL-rearranged AML seem to benefit from allogeneic transplantation in first CR.


2015 ◽  
Vol 7 ◽  
pp. BIC.S19614 ◽  
Author(s):  
Marwa H. Saied ◽  
Jacek Marzec ◽  
Sabah Khalid ◽  
Paul Smith ◽  
Gael Molloy ◽  
...  

Trisomy 8 acute myeloid leukemia (AML) is the commonest numerical aberration in AML. Here we present a global analysis of trisomy 8 AML using methylated DNA immunoprecipitation-sequencing (MeDIP-seq). The study is based on three diagnostic trisomy 8 AML and their parallel relapse status in addition to nine non-trisomic AML and four normal bone marrows (NBMs). In contrast to non-trisomic DNA samples, trisomy 8 AML showed a characteristic DNA methylation distribution pattern because an increase in the frequency of the hypermethylation signals in chromosome 8 was associated with an increase in the hypomethylation signals in the rest of the chromosomes. Chromosome 8 hypermethylation signals were found mainly in the CpG island (CGI) shores and interspersed repeats. Validating the most significant differentially methylated CGI ( P = 7.88 · 10–11identified in trisomy 8 AML demonstrated a specific core region within the gene body of HHEX, which was significantly correlated with HHEX expression in both diagnostic and relapse trisomy 8 AMLs. Overall, the existence of extra chromosome 8 was associated with a global impact on the DNA methylation distribution with identification of HHEX gene methylation as a potential diagnostic marker for trisomy 8 AML.


Author(s):  
Salil N. Vaniawala ◽  
Monika V. Patel ◽  
Pratik D. Chavda ◽  
Shivangi H. Zaveri ◽  
Pankaj K. Gadhia

Background: Acute myeloid leukemia (AML) is a heterogeneous disorder that results from a block in the differentiation of haematopoietic progenitor cells along with uncontrolled proliferation. Trisomy 8 is the most common recurring numerical chromosomal aberrations in acute myeloid leukemia (AML). It occurs either as a sole anomaly or together with other additional chromosomal aberrations. The prognostic significance of trisomy 8 in presence of other additional chromosomal abnormality depends on clonal cytogenetic changes. The patients with trisomy 8 had shorter survival with significantly increased risk with other chromosomal abnormality.Methods: Total 139 patients were screened between January 2016 to November 2016 who were suspected of AML cases. Bone marrow cultures were set up using conventional cytogenetic methods. Chromosomal preparation was made and subjected to GTG banding technique. Banded metaphases were analysed and karyotyped for further analysis.Results: Cytogenetic evaluation of karyotyped of 139 suspected AML patients showed 52 with t(8;21)(q22;q22), 36 with t(15;17)(q22;q12), and 11 with inv(16)(p13;q22). The rest 40 cases found with additional chromosomal abnormalities, of which 16 were sole trisomy 8 and 24 cases were found with other chromosomal abnormalities In addition, only one person found with t(8;21) and trisomy 8, while  three person having t(15;17) with trisomy 8.Conclusions: AML is considered to be one of the most important cytogenetic prognostic determinants. Recurrent chromosomal translocation with trisomy 8 varying 1.9% for t(8;21) and 8.3% for t(15;17). In the present study trisomy 8 in AML with known favourable anomalies is very small. Therefore, it cannot be taken as a prognostic marker.


Blood ◽  
2010 ◽  
Vol 116 (17) ◽  
pp. 3147-3156 ◽  
Author(s):  
Jacob M. Rowe ◽  
Martin S. Tallman

AbstractMore than one quarter of a million adults throughout the world are diagnosed annually with acute myeloid leukemia (AML). Despite considerable progress during the past 3 decades in the therapy of AML, two-thirds of young adults and 90% of older adults still die of their disease. The reported median age has increased over the past few decades, mostly because of a greater willingness of physicians to diagnose and treat older patients, and now is 72 years. The greatest challenge is in this age group. However, much improvement in therapy is needed for all adults with AML. Recent advances in allogeneic transplantation, a better understanding of prognostic factors, and development of targeted agents have only modestly improved overall outcome when large populations of patients are considered. Although an explosion in knowledge about the molecular pathogenesis of AML has outpaced treatment advances, such insights hold promise for the development of new therapies directed at specific molecular abnormalities that perturb malignant cell survival pathways. The current approach in 2010 to the management of this disease is presented through a discussion of illustrative cases.


HemaSphere ◽  
2020 ◽  
Vol 4 (1) ◽  
pp. e326
Author(s):  
Madlen Jentzsch ◽  
Juliane Grimm ◽  
Marius Bill ◽  
Karoline Goldmann ◽  
Julia Schulz ◽  
...  

Blood ◽  
2008 ◽  
Vol 111 (6) ◽  
pp. 3183-3189 ◽  
Author(s):  
Ramiro Garzon ◽  
Stefano Volinia ◽  
Chang-Gong Liu ◽  
Cecilia Fernandez-Cymering ◽  
Tiziana Palumbo ◽  
...  

Abstract MicroRNAs (miRNAs) are small RNAs of 19 to 25 nucleotides that are negative regulators of gene expression. To determine whether miRNAs are associated with cytogenetic abnormalities and clinical features in acute myeloid leukemia (AML), we evaluated the miRNA expression of CD34+ cells and 122 untreated adult AML cases using a microarray platform. After background subtraction and normalization using a set of housekeeping genes, data were analyzed using Significance Analysis of Microarrays. An independent set of 60 untreated AML patients was used to validate the outcome signatures using real-time polymerase chain reaction. We identified several miRNAs differentially expressed between CD34+ normal cells and the AML samples. miRNA expression was also closely associated with selected cytogenetic and molecular abnormalities, such as t(11q23), isolated trisomy 8, and FLT3-ITD mutations. Furthermore, patients with high expression of miR-191 and miR-199a had significantly worse overall and event-free survival than AML patients with low expression (overall survival: miR-191, P = .03; and miR-199a, P = .001, Cox regression). In conclusion, miRNA expression in AML is closely associated with cytogenetics and FLT3-ITD mutations. A small subset of miRNAs is correlated with survival.


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