Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA)

Preudhomme, Claude; Sagot, C.; Boissel, Nicolas; Cayuela, Jean‐Michel; Tigaud, Isabelle; Botton, Stéphane de; Thomas, Xavier; Raffoux, Emmanuel; Lamandin, Charlotte; Castaigné, Sylvie; Fenaux, Pierre; Dombret, Hervé

doi:10.1182/blood-2002-03-0990

Cited by 468 publications

(355 citation statements)

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“…It was significantly lower in CEBPA-mut group than in CEBPA-wt group (means 536.1 and 729.4 respectively, p = 0.039). This result agreed with some previous reports [17,18,20]. However, Frohling et al [21] reported no significant difference in LDH level between both groups.…”

Section: Discussionsupporting

confidence: 93%

“…Similarly there was non-significant difference in gender distribution between both groups. This finding is in accordance with previous studies [17,18]. Though, Green et al [19] found that younger age was associated with a greater number of mutations.…”

Section: Discussionsupporting

confidence: 93%

“…The prevalence of M2 in CEBPA mutated AML was agreed by most of the previous studies [14,23,24,25]. However, others reported M1 as the mostly occurring FAB subtypes in CEBPA mutated AML [17,26,27].…”

Section: Discussionsupporting

confidence: 78%

“…All the detected mutations were single mutations (3 in each b-ZIP, and TAD-2 regions and 1 in TAD-1 region). In previous studies, the incidence of CEBPA mutation in AML varies * Relapse is calculated out of the cases who achieve CR # Significance Log rank from 11 to 20 % with the CN-AML category having a higher incidence [10,16,17]. The absence of double CEBPA mutation within our patients may be partly due to low sample number or the limited ability of fragment analysis assay to detect point mutations that will not lead to change in the PCR product fragment length.…”

Section: Discussionmentioning

confidence: 95%

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Prevalence and Prognostic Impact of CEBPA Gene Mutation (Simplified Assay Technique) in Egyptian Acute Myeloid Leukemia Patients with Normal Cytogenetics

Said

El‐Masry

Salem

et al. 2015

Indian J Hematol Blood Transfus

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Mutations of the CCAAT/enhancer binding protein alpha (CEBPA) gene have been associated with a favorable outcome in patients with acute myeloid leukemia (AML), especially in those with a normal cytogenetics. However, few studies were done on Egyptian AML patients and none of them look for easier and less expensive method for CEBPA mutation screening. This study is aimed to investigate the prevalence of CEBPA mutations and its clinical and prognostic impact in Egyptian patients with cytogenetically normal AML (CN-AML). This was done using fragment analysis to assess this method as a cheaper and less laborious screening method compared to sequencing. Fluorescent PCR was done to amplify CEBPA gene in DNA extracted from 40 CN-AML patients. This was followed by fragment analysis of post-PCR products using GeneMapper software for detection of CEBPA mutations. CEBPA gene mutations were found in 7/40 CN-AML patients (17.5 %) and it was significantly associated with lower LDH levels (p = 0.039). All patients with CEBPA mutations achieved clinical remission and none of them showed refractoriness, relapsed, or died by the end of the 2 years study period. Furthermore, those patients demonstrate significantly longer overall and disease free survival than those with wild type CEBPA gene (p = 0.001 and 0.004 respectively). CEBPA mutation has a favorable prognostic impact in CN-AML. Fragment analysis is a good, lees laborious and cheaper method that can be used for CEBPA mutation screening in patients with CN-AML.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 95%

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Prevalence and Prognostic Impact of CEBPA Gene Mutation (Simplified Assay Technique) in Egyptian Acute Myeloid Leukemia Patients with Normal Cytogenetics

Said

El‐Masry

Salem

et al. 2015

Indian J Hematol Blood Transfus

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“…Internal tandem duplications (ITDs) in the FMS-like tyrosine kinase-3 (FLT3) gene,12 partial tandem duplications in the mixed lineage leukemia gene (MLL)34 and enhanced expression of replication factor ectopic virus integration site 15 are all indicators of poor prognosis. In turn, mutation in replication factor CCAAT/enhancer-banding protein α (CEBPA) is associated with good response to therapy 67. With current karyotyping methods, no chromosomal abnormality is found in 40% to 50% of AML patients, and differentiation between different prognostic subtypes in this group of patients by present approaches to molecular genetics seems to be of great importance 489.…”

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confidence: 99%

Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia

Pazhakh

Zaker

Atashrazm

2011

Annals of Saudi Medicine

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BACKGROUND AND OBJECTIVES:Nucleophosmin gene mutations are frequently reported in acute myeloid leukemia (AML) patients with normal karyotype, which is also frequently associated with internal tandem duplication mutations in the FMS-like tyrosine kinase-3 gene. We sought to detect the nucleophosmin and FMS-like tyrosine kinase-3 (FLT3) internal tandem duplication (ITD) mutations among Iranian patients with AML and to assess the relationship between these mutations and the subtypes of the disease.DESIGN AND SETTING:Cross-sectional study of patients referred during 2007 through 2009.PATIENTS AND METHODS:Bone marrow and peripheral blood samples of 131 AML patients were randomly collected at the time of diagnosis and prior to treatment and the DNA extracted. After amplifying the nucleophosmin and FLT3 gene regions, positive cases were screened by conformation-sensitive gel electrophoresis and agarose gel electrophoresis techniques.RESULTS:Of 131 patients, 23 (17.5%) (0.95% CI=0.107-0.244) had nucleophosmin gene mutations. The highest frequency of such mutations was found among the subtypes of M4 (30.4%), M3 (21.7%) and M5 (17.4%). There was a high frequency of these mutations in the M3 subtype as well as a high frequency of allele D in all subtypes. Also, 21 (16.0%) samples (0.95% CI=0.092-0.229) had FLT3/ITD mutation, of which 8 samples had mutant nucleophosmin (8 of 23, 35%), and another 13 samples had wild-type nucleophosmin gene (13 of 108, 12%). There was a high degree of association between the occurrence of nucleophosmin and FLT3/ITD mutations (P=.012).CONCLUSION:Our data showed a high frequency of NPM1 mutations in the monocytic subtypes of AML, as well as a high degree of association between the occurrence of NPM1 and FLT3/ITD mutations.

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Diagnosis and Classification of Acute Leukaemia

Bain¹

2005

Postgraduate Haematology

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Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the Acute Leukemia French Association (ALFA)

Cited by 468 publications

References 17 publications

Prevalence and Prognostic Impact of CEBPA Gene Mutation (Simplified Assay Technique) in Egyptian Acute Myeloid Leukemia Patients with Normal Cytogenetics

Prevalence and Prognostic Impact of CEBPA Gene Mutation (Simplified Assay Technique) in Egyptian Acute Myeloid Leukemia Patients with Normal Cytogenetics

Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia

Diagnosis and Classification of Acute Leukaemia

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