Molecular Profiling Defines Distinct Prognostic Subgroups in Childhood AML: A Report From the French ELAM02 Study Group

Marceau-Renaut, Alice; Duployez, Nicolas; Ducourneau, Benoît; Labopin, Myriam; Petit, Arnaud; Rousseau, Alexandra; Geffroy, Sandrine; Bucci, Maria Pia; Cuccuini, Wendy; Fenneteau, Odile; Ruminy, Philippe; Nelken, Brigitte; Ducassou, Stéphane; Gandemer, Virginie; Leblanc, Thierry; Gautier, Michel; Bertrand, Yves; Baruchel, André; Leverger, Guy; Preudhomme, Claude; Lapillonne, Hélène

doi:10.1097/hs9.0000000000000031

Cited by 48 publications

(59 citation statements)

References 30 publications

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“…Further studies are needed to extend those findings and determine whether the LSC17 score has any association with other molecular aberrations. Importantly, the LSC17 score retained a strong value in AML without favorable and adverse molecular-risk factors as previously defined by our group [ 1 ] as well as in cytogenetically normal-AML which makes up respectively 50% and 25% of all pediatric AML. This is critical in routine practice since these AML categories have been shown to display heterogeneous outcome.…”

supporting

confidence: 70%

“…Major advances have been made do better define the genetic basis of AML. Underlying cytogenetic and molecular aberrations are now routinely used to inform disease classification and stratify patients into favorable, unfavorable or intermediate risk categories, the latter encompassing about a half of patients [ 1 ]. Although outcome has greatly improved over the past decade, relapse occurs in about 30% of pediatric AML and represents the major cause of mortality.…”

mentioning

confidence: 99%

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A 17-gene-expression profile to improve prognosis prediction in childhood acute myeloid leukemia

Duployez

Preudhomme

Cheok³

2018

Oncotarget

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supporting

confidence: 70%

mentioning

confidence: 99%

A 17-gene-expression profile to improve prognosis prediction in childhood acute myeloid leukemia

Duployez

Preudhomme

Cheok³

2018

Oncotarget

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“…A report from the French study group con rmed that WT1 mutations were an independent prognostic factor for pediatric AML. 22 However, a report from the Japanese study group showed that WT1 mutations were related to a poor prognosis in patients with normal cytogenetics, excluding those with FLT3/ITD and those younger than 3 years. 23 By contrast, a report from the Nordic Society of Pediatric Hematology and Oncology (NOPHO) revealed that no signi cant correlation with survival was seen for WT1 mutations.…”

Section: Discussionmentioning

confidence: 99%

Wilms Tumor 1 Mutations are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia

Wang

Weng

Zhou

et al. 2020

Preprint

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Background: The role of Wilms tumor 1 (WT1) mutations remains controversial for patients with acute myeloid leukemia (AML) with regard to the prognostic impact. Here, we aimed to determine the clinical implication of WT1 mutations in a large cohort of pediatric AML. Methods: The clinical data of 870 pediatric patients with AML were downloaded from the therapeutically applicable research to generate effective treatment (TARGET) dataset. We analyzed the prevalence, clinical profile and prognosis of WT1 mutations in these patients. Results: WT1 mutations were founded in 6.7% of total patients. WT1 mutations were closely associated with normal cytogenetics (P<0.001), FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) mutations (P<0.001), and low complete remission induction rates (P<0.01). Compared to patients without WT1 mutations, patients with WT1 mutations had worse 5-year event-free survival (21.7±5.5% vs 48.9±1.8%, P<0.001) and overall survival (41.4±6.6% vs 64.3±1.7%, P<0.001). Moreover, patients with both WT1 and FLT3/ITD mutations had a dismal prognosis. Compared to chemotherapy alone, hematopoietic stem cell transplantation had a tendency to improve prognoses of WT1-mutated patients. In multivariate analysis, WT1 mutations conferred an independent adverse impact on event-free survival (hazard ratio 1.910, P = 0.001) and overall survival (hazard ratio 1.709, P = 0.020). Conclusion: Our findings demonstrate that WT1 mutations are independent poor prognostic factors in pediatric AML.

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“…However, as noted above, there are significant differences in genetic alterations between adult and pediatric patients with AML. Previous larger studies suggested that current guidelines, including the ELN guidelines, are not adequate for children with AML (14,32,33), thus, there is a need for the development of a pediatric-specific guidelines for more precise stratification.…”

Section: Discussionmentioning

confidence: 99%

Panel‑based next‑generation sequencing facilitates the characterization of childhood acute myeloid leukemia in clinical settings

Ishida

Iguchi

et al. 2020

Biomed Rep

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Acute myeloid leukemia (AML) accounts for ~20% of pediatric leukemia cases. The prognosis of pediatric AML has been improved in recent decades, but it trails that of most other types of pediatric cancer, with mortality rates of 30-40%. Consequently, newer more targeted drugs are required for incorporation into treatment plans. These newer drugs selectively target AML cells with specific gene alterations. However, there are significant differences in genetic alterations between adult and pediatric patients with AML. In the present study, inexpensive and rapid next-generation sequencing (NGS) of >150 cancer-related genes was performed for matched diagnostic, remission and relapse (if any) samples from 27 pediatric patients with AML. In this analysis, seven genes were recurrently mutated. KRAS was mutated in seven patients, NRAS was mutated in three patients, and KIT, GATA1, WT1, PTPN11, JAK3 and FLT3 were each mutated in two patients. Among patients with relapsed AML, six harbored KRAS mutations at diagnosis; however, four of these patients lost these mutations at relapse. Additionally, two genetic alterations (FLT3-ITD and TP53 alterations) were detected among patients who eventually relapsed, and these mutations are reported to be adverse prognostic factors for adult patients with AML. This panel-based, targeted sequencing approach may be useful in determining the genetic background of pediatric AML and improving the prediction of treatment response and detection of potentially targetable gene alterations. RAS pathway mutations were highly unstable at relapse; therefore, these mutations should be chosen as a target with caution. Incorporating this panel-based NGS approach into the clinical setting may allow for a patient-oriented strategy of precision treatment for childhood AML.

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Molecular Profiling Defines Distinct Prognostic Subgroups in Childhood AML: A Report From the French ELAM02 Study Group

Abstract: Supplemental Digital Content is available in the text

Cited by 48 publications

References 30 publications

A 17-gene-expression profile to improve prognosis prediction in childhood acute myeloid leukemia

A 17-gene-expression profile to improve prognosis prediction in childhood acute myeloid leukemia

Wilms Tumor 1 Mutations are Independent Poor Prognostic Factors in Pediatric Acute Myeloid Leukemia

Panel‑based next‑generation sequencing facilitates the characterization of childhood acute myeloid leukemia in clinical settings

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