The clinical relevance of BAALC and ERG expression levels in pediatric AML

Hermkens, Malou; Heuvel‐Eibrink, Marry M. van den; Arentsen-Peters, Susan T.C.J.M.; Baruchel, André; Starý, Jan; Reinhardt, Dirk; Zimmerman, Michael T.; Haas, Valérie de; Pieters, Rob; Zwaan, C. Michel

doi:10.1038/leu.2012.233

Cited by 12 publications

(12 citation statements)

References 13 publications

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“…These findings are parallel to that reported by Eid et al [25] and Hovland et al [24] Haferlach et al [29]. On the other hand, high BAALC and ERG expression levels did not have independent prognostic significance in pediatric AML cohort or in the CN-AML subgroup specifically in the study done by Hermkens et al [30]. This might be related to ethnic origin of the patients studied.…”

Section: Discussionsupporting

confidence: 88%

“…AML constitutes 15-20 % of childhood leukemia and has an overall survival (OS) of 70 %. The prognosis has improved over the past couple of decades through optimization of treatment protocols, in which identification of disease subgroups that are based on genetic markers has turned out to be essential [1].…”

Section: Introductionmentioning

confidence: 99%

“…In order to refine risk stratification of pediatric CN-AML, it is important to study the underlying molecular aberrations [1].…”

Section: Introductionmentioning

confidence: 99%

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The Prognostic Relevance of BAALC and ERG Expression Levels in Cytogenetically Normal Pediatric Acute Myeloid Leukemia

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Khodary

Zeed

et al. 2014

Indian J Hematol Blood Transfus

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Cytogenetic aberrations are important prognostic factors in acute myeloid leukemia (AML). About 45 % of de novo adult AML and 20 % of pediatric AML lack cytogenetic abnormalities, so identification of predictive molecular markers might improve therapy. Mutation status of FLT3, NPM1 genes and gene expression levels of ERG, BAALC have been postulated as possible prognostic markers in pediatric AML with normal karyotype. Pretreatment blood samples from 47 cytogenetically normal AML patients were analysed for BAALC and ERG expression using real time RT-PCR. The patients were dichotomized at BAALC and ERG mean expression into low and high expression based on the median expression as cutoff. BAALC showed high expression in (24/47; 51.1 %) of patients and ERG high expression was detected in (22/ 47; 46.6 %). With follow-up for 1 year, patients with high BAALC and high ERG had inferior EFS (P = 0.001, P = 0.017 respectively), overall survival (P = 0.001, 0.08 respectively), and low rates of induction remission (P = 0.001, P = 0.0017 respectively) as compared to those with low expression. Also there was significant positive association between high expression of BAALC; ERG and FLT-ITD mutations (P = 0.016; P = 0.007 respectively). Multivariable analysis confirmed that high BAALC expression is an independent risk factor for EFS [HR for EFS 1.9(1.04-3.46) P = 0.037]; and OS [HR OS 1.55(1.7-3.36) P = 0.03]. In conclusion: Over expression of BAALC could predict adverse clinical outcome and may define important risk factor in cytogenetically normal pediatric AML.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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The Prognostic Relevance of BAALC and ERG Expression Levels in Cytogenetically Normal Pediatric Acute Myeloid Leukemia

Aref

Khodary

Zeed

et al. 2014

Indian J Hematol Blood Transfus

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“…A remote GATA2 hematopoietic enhancer alteration in inv(3)(q21;q26) by activating EVI1 expression was reported [ 28 ]. It is believed that the expression level of these genes is negatively associated with the treatment outcome of AML [ 29 – 33 ]; however, the results are controversial between western and eastern countries especially for BAALC and ERG [ 34 , 35 ]. The role of some new gene markers, such as MEIS1 , which is up-regulated by MLL abnormalities, still needs to be addressed in AML [ 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Gene mutational pattern and expression level in 560 acute myeloid leukemia patients and their clinical relevance

et al. 2017

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BackgroundCytogenetic aberrations and gene mutations have long been regarded as independent prognostic markers in AML, both of which can lead to misexpression of some key genes related to hematopoiesis. It is believed that the expression level of the key genes is associated with the treatment outcome of AML.MethodsIn this study, we analyzed the clinical features and molecular aberrations of 560 newly diagnosed non-M3 AML patients, including mutational status of CEBPA, NPM1, FLT3, C-KIT, NRAS, WT1, DNMT3A, MLL-PTD and IDH1/2, as well as expression levels of MECOM, ERG, GATA2, WT1, BAALC, MEIS1 and SPI1.ResultsCertain gene expression levels were associated with the cytogenetic aberration of the disease, especially for MECOM, MEIS1 and BAALC. FLT3, C-KIT and NRAS mutations contained conversed expression profile regarding MEIS1, WT1, GATA2 and BAALC expression, respectively. FLT3, DNMT3A, NPM1 and biallelic CEBPA represented the mutations associated with the prognosis of AML in our group. Higher MECOM and MEIS1 gene expression levels showed a significant impact on complete remission (CR) rate, disease free survival (DFS) and overall survival (OS) both in univariate and multivariate analysis, respectively; and an additive effect could be observed. By systematically integrating gene mutational status results and gene expression profile, we could establish a more refined system to precisely subdivide AML patients into distinct prognostic groups.ConclusionsGene expression abnormalities contained important biological and clinical informations, and could be integrated into current AML stratification system.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1279-4) contains supplementary material, which is available to authorized users.

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“…Furthermore, in acute T cell-lymphoblastic leukemia (T-ALL) patients, a high level of ERG expression has been associated with poor relapse-free survival (RFS) (15,16). In childhood AML, the impact of ERG expression level is somewhat controversial: Pigazzi et al (17) suggested that high ERG expression was an independent unfavorable prognostic marker for childhood myeloid leukemia, whereas the study by Hermkens et al did not find such correlation (18).…”

Section: Introductionmentioning

confidence: 99%

ETS-related gene is a novel prognostic factor in childhood acute lymphoblastic leukemia

et al. 2016

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Abstract. The ETS-related gene (ERG) has been demonstrated to be associated with overall survival in cytogenetically normal acute myeloid leukemia and acute T cell-lymphoblastic leukemia (T-ALL) in adult patients. However, there are no data available regarding the impact of ERG expression on childhood ALL. In the present study, ERG expression levels were analyzed in bone marrow samples from 119 ALL pediatric patients. ALL patients demonstrated higher ERG expression compared with the controls (P<0.0001). In addition, low ERG expression identified a group of patients with higher white blood cell counts (P=0.011), higher percentages of T-ALL immunophenotype (P=0.027), and higher relapse rates (P=0.009). Survival analyses demonstrated that low ERG expression was associated with inferior relapse-free survival (RFS) in childhood ALL (P=0.036) and was an independent prognostic factor in multivariable analyses for RFS. In conclusion, low ERG expression is associated with poor outcomes and may be used to serve as a molecular prognostic marker to identify patients with a high risk of relapse in childhood ALL.

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The clinical relevance of BAALC and ERG expression levels in pediatric AML

Cited by 12 publications

References 13 publications

The Prognostic Relevance of BAALC and ERG Expression Levels in Cytogenetically Normal Pediatric Acute Myeloid Leukemia

The Prognostic Relevance of BAALC and ERG Expression Levels in Cytogenetically Normal Pediatric Acute Myeloid Leukemia

Gene mutational pattern and expression level in 560 acute myeloid leukemia patients and their clinical relevance

ETS-related gene is a novel prognostic factor in childhood acute lymphoblastic leukemia

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