<i>BAALC</i> Expression and <i>FLT3</i> Internal Tandem Duplication Mutations in Acute Myeloid Leukemia Patients With Normal Cytogenetics: Prognostic Implications

Baldus, Claudia D.; Thiede, Christian; Soucek, Silke; Bloomfield, Clara D.; Thiel, Eckhard; Ehninger, Gerhard

doi:10.1200/jco.2005.01.6253

Cited by 154 publications

(151 citation statements)

References 21 publications

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“…Moreover, FLT3-ITD has been found to be an independent prognostic factor for OS, and CRD in CN-AML. 5,7,35 However, in other cytogenetic subsets including t(15;17) AML, FLT3-ITD appears not to be an independent prognostic factor. 36,37 The molecular characteristics of FLT3-ITD are extremely variable among patients.…”

Section: Flt3mentioning

confidence: 99%

Cooperating gene mutations in acute myeloid leukemia: a review of the literature

et al. 2008

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Acute myeloid leukemia (AML) is a heterogeneous group of neoplastic disorders with great variability in clinical course and response to therapy, as well as in the genetic and molecular basis of the pathology. Major advances in the understanding of leukemogenesis have been made by the characterization and the study of acquired cytogenetic abnormalities, particularly reciprocal translocations observed in AML. Besides these major cytogenetic abnormalities, gene mutations also constitute key events in AML pathogenesis. In this review, we describe the contribution of known gene mutations to the understanding of AML pathogenesis and their clinical significance. To gain more insight in this understanding, we clustered these alterations in three groups: (1) mutations affecting genes that contribute to cell proliferation (FLT3, c-KIT, RAS, protein tyrosine standard phosphatase nonreceptor 11); (2) mutations affecting genes involved in myeloid differentiation (AML1 and CEBPA) and (3) mutations affecting genes implicated in cell cycle regulation or apoptosis (P53, NPM1). This nonexhaustive review aims to show how gene mutations interact with each other, how they contribute to refine prognosis and how they can be useful for risk-adapted therapeutic management of AML patients.

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Section: Flt3mentioning

confidence: 99%

Cooperating gene mutations in acute myeloid leukemia: a review of the literature

et al. 2008

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“…Importantly, FLT3-ITD has been found to constitute an independent prognostic factor for CRD Bienz et al, 2005), cumulative incidence of relapse (CIR; Baldus et al, 2006a) and OS (Bienz et al, 2005;Baldus et al, 2006a). Ozeki et al (2004) reported high expression levels of FLT3-WT allele, resulting in protein tyrosine autophosphorylation and similar sensitivity to the FLT3 inhibitor as FLT3-ITD, in some AML patients without FLT3-ITD or FLT3-TKD.…”

Section: Review ª 2007 the Authorsmentioning

confidence: 99%

“…These include gene mutations, such as the internal tandem duplication (ITD) of the FLT3 gene (Nakao et al, 1996;Kottaridis et al, 2001;Whitman et al, 2001;Fröhling et al, 2002;Kainz et al, 2002;Schnittger et al, 2002;Thiede et al, 2002;Beran et al, 2004), the partial tandem duplication (PTD) of the MLL gene (Schichman et al, 1994;Caligiuri et al, 1998;Schnittger et al, 2000;Döhner et al, 2002;Shiah et al, 2002;Muñoz et al, 2003), and mutations of the CEBPA (Pabst et al, 2001;Preudhomme et al, 2002;Fröhling et al, 2004) and NPM1 genes (Boissel et al, 2005;Döhner et al, 2005;Falini et al, 2005;Schnittger et al, 2005;Suzuki et al, 2005;Thiede et al, 2006) (Fig 1). Likewise, adverse prognosis has been associated with overexpression of single genes, such as BAALC (Tanner et al, 2001;Baldus et al, 2003Baldus et al, , 2006aBienz et al, 2005), ERG and MN1 (Heuser et al, 2006). Recent studies have also evaluated the usefulness of global gene-expression profiling to identify prognostic subgroups within the heterogeneous group of CN-AML patients (Bullinger et al, 2004;Valk et al, 2004;Radmacher et al, 2006).…”

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confidence: 99%

Clinical outcome of de novo acute myeloid leukaemia patients with normal cytogenetics is affected by molecular genetic alterations: a concise review

et al. 2007

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SummaryNormal cytogenetics are detected pretreatment in approximately 45% of patients with de novo acute myeloid leukaemia (AML); thus this constitutes the single largest cytogenetic group of AML. Recently, molecular genetic alterations with prognostic significance have been reported in these patients. They include internal tandem duplication of the FLT3 gene, partial tandem duplication of the MLL gene, mutations of the CEBPA and NPM1 genes and aberrant expression of the BAALC, ERG and MN1 genes. Additionally, gene-expression profiling has been applied to identify prognostically relevant subgroups. Substantial progress has been made in the understanding of molecular pathways deregulated in leukaemogenesis and how these defects can be targeted by novel therapeutic compounds. Here we critically review the molecular heterogeneity among AML patients with normal cytogenetics and discuss how these data may translate into a prognostic, molecular-based treatment stratification that may improve the currently unsatisfactory outcome of these patients.

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“…This result is in agreement with that of Paschka et al [11] and Virappane et al [8] who found that mutations in the WT1 gene are independent predictors for worse DFS and OS in CN-AML. The effect of WT1 mutation on patient's survival could be explained on the basis that patients with mutated WT1 have high expressers of ERG and BAALC more frequently than patients with unmutated WT1 [12]. Over expression of both the ERG and the BAALC genes has been associated with an adverse prognosis.…”

Section: Discussionmentioning

confidence: 99%

Prognostic relevance of Wilms tumor 1 (WT1) gene Exon 7 mutations in-patient with cytogenetically normal acute myeloid leukemia

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Sharawy

Sabry

et al. 2013

Indian J Hematol Blood Transfus

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This study aimed to assess the prognostic influences of Wilms tumor 1 (WT1) gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML) among Egyptian patients. Exon 7 of WT1 was screened for mutations in samples from 82 CN-AML patients out of 203 newly diagnosed AML patients, using a high-resolution capillary electrophoresis. Seven out of 82 AML patients (8.3 %) harbored WT1 mutations. There was no significant difference between the mutant WT1 and wild type AML patients as regard age, sex, French-AmericanBritish subtypes and the prevalence of success of induction remission therapy (P \ 0.5). AML patients with mutant WT1 had shorter overall survival as compared to those patients with wild WT1 (HR = 1.38; 95 % CI 4.79-6.86; P = 0.004). In conclusion, CN-AML patients with WT1 gene mutation have poor clinical outcome. We recommend testing the WT1 mutations as part of molecularly based risk assessment and risk-adapted treatment stratification of patients with CN-AML.

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BAALC Expression and FLT3 Internal Tandem Duplication Mutations in Acute Myeloid Leukemia Patients With Normal Cytogenetics: Prognostic Implications

Abstract: This study strengthens BAALC expression as one of the most important prognostic factors in AML patients with normal cytogenetics. BAALC expression and FLT3 mutation status should assist in tailoring induction and postremission therapies.

Cited by 154 publications

References 21 publications

Cooperating gene mutations in acute myeloid leukemia: a review of the literature

Cooperating gene mutations in acute myeloid leukemia: a review of the literature

Clinical outcome of de novo acute myeloid leukaemia patients with normal cytogenetics is affected by molecular genetic alterations: a concise review

Prognostic relevance of Wilms tumor 1 (WT1) gene Exon 7 mutations in-patient with cytogenetically normal acute myeloid leukemia

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