The stem cell-associated gene expression signature allows risk stratification in pediatric acute myeloid leukemia

Leukemia ◽  
2018 ◽  
Vol 33 (2) ◽  
pp. 348-357 ◽  
Author(s):  
Nicolas Duployez ◽  
Alice Marceau-Renaut ◽  
Céline Villenet ◽  
Arnaud Petit ◽  
Alexandra Rousseau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Risk Stratification ◽  
Myeloid Leukemia ◽  
Gene Expression Signature ◽  
Pediatric Acute Myeloid Leukemia ◽  
Expression Signature ◽  
Acute Myeloid

NUP98-PHF23 fusion is recurrent in acute myeloid leukemia and shares gene expression signature of leukemic stem cells

2016 ◽  
Vol 45 ◽  
pp. 1-7 ◽  
Author(s):  
Hao Ho ◽  
Alyza M. Skaist ◽  
Aparna Pallavajjala ◽  
Raluca Yonescu ◽  
Denise Batista ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Expression Signature ◽  
Leukemic Stem Cells ◽  
Expression Signature ◽  
Acute Myeloid

scholarly journals High BAALC expression associates with other molecular prognostic markers, poor outcome, and a distinct gene-expression signature in cytogenetically normal patients younger than 60 years with acute myeloid leukemia: a Cancer and Leukemia Group B (CALGB) study

Blood ◽  
2008 ◽  
Vol 111 (11) ◽  
pp. 5371-5379 ◽  
Author(s):  
Christian Langer ◽  
Michael D. Radmacher ◽  
Amy S. Ruppert ◽  
Susan P. Whitman ◽  
Peter Paschka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Prognostic Factor ◽  
Myeloid Leukemia ◽  
Gene Expression Signature ◽  
Specific Gene ◽  
Stem Cell Markers ◽  
Inverse Association ◽  
Expression Signature ◽  
Acute Myeloid

AbstractBAALC expression is considered an independent prognostic factor in cytogenetically normal acute myeloid leukemia (CN-AML), but has yet to be investigated together with multiple other established prognostic molecular markers in CN-AML. We analyzed BAALC expression in 172 primary CN-AML patients younger than 60 years of age, treated similarly on CALGB protocols. High BAALC expression was associated with FLT3-ITD (P = .04), wild-type NPM1 (P < .001), mutated CEBPA (P = .003), MLL-PTD (P = .009), absent FLT3-TKD (P = .005), and high ERG expression (P = .05). In multivariable analysis, high BAALC expression independently predicted lower complete remission rates (P = .04) when adjusting for ERG expression and age, and shorter survival (P = .04) when adjusting for FLT3-ITD, NPM1, CEBPA, and white blood cell count. A gene-expression signature of 312 probe sets differentiating high from low BAALC expressers was identified. High BAALC expression was associated with overexpression of genes involved in drug resistance (MDR1) and stem cell markers (CD133, CD34, KIT). Global microRNA-expression analysis did not reveal significant differences between BAALC expression groups. However, an analysis of microRNAs that putatively target BAALC revealed a potentially interesting inverse association between expression of miR-148a and BAALC. We conclude that high BAALC expression is an independent adverse prognostic factor and is associated with a specific gene-expression profile.

scholarly journals An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4193-4201 ◽  
Author(s):  
Klaus H. Metzeler ◽  
Manuela Hummel ◽  
Clara D. Bloomfield ◽  
Karsten Spiekermann ◽  
Jan Braess ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Score ◽  
Gene Expression Signature ◽  
Event Free Survival ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Expression Signature ◽  
Acute Myeloid

Abstract Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene-expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AMLCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes), which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P = .002), event-free survival (HR = 1.73; P = .001), and relapse-free survival (HR = 1.76; P = .025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD, and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR = 4.11; P < .001), event-free survival (HR = 2.90; P < .001), and relapse-free survival (HR = 3.14, P < .001) and retained its significance in a multivariate model for OS. In summary, we present a novel gene-expression signature that offers additional prognostic information for patients with CN-AML.

Abstract 2243: Gene expression signature of aneuploidy in acute myeloid leukemia

2014 ◽  
Author(s):  
Giorgia Simonetti ◽  
Antonella Padella ◽  
Viviana Guadagnuolo ◽  
Cristina Papayannidis ◽  
Francesca Volpato ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Expression Signature ◽  
Expression Signature ◽  
Acute Myeloid

scholarly journals Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification?

Blood ◽  
2006 ◽  
Vol 109 (2) ◽  
pp. 431-448 ◽  
Author(s):  
Krzysztof Mrózek ◽  
Guido Marcucci ◽  
Peter Paschka ◽  
Susan P. Whitman ◽  
Clara D. Bloomfield
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Tandem Duplication ◽  
Gene Mutations ◽  
Gene Expression Signature ◽  
Genetic Alterations ◽  
Expression Signature ◽  
Cytogenetically Normal Aml ◽  
Acute Myeloid

Abstract Recent molecular analyses of leukemic blasts from pretreatment marrow or blood of patients with acute myeloid leukemia (AML) and a normal karyotype, the largest cytogenetic subset (ie, 40%-49%) of AML, have revealed a striking heterogeneity with regard to the presence of acquired gene mutations and changes in gene expression. Multiple submicroscopic genetic alterations with prognostic significance have been discovered, including internal tandem duplication of the FLT3 gene, mutations in the NPM1 gene, partial tandem duplication of the MLL gene, high expression of the BAALC gene, and mutations in the CEBPA gene. Application of gene-expression profiling has also identified a gene-expression signature that appears to separate cytogenetically normal AML patients into prognostic subgroups, although gene-expression signature-based classifiers predicting outcome for individual patients with greater accuracy are needed. These and similar future findings are likely to have a major impact on the clinical management of cytogenetically normal AML not only in prognostication but also in selection of appropriate treatment, since many of the identified genetic alterations already constitute or will potentially become targets for specific therapeutic intervention. In this report, we review prognostic genetic findings in karyotypically normal AML and discuss their clinical implications.

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