NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study

Asnafi, Vahid; Buzyn, Agnès; Noir, Sandrine Le; Baleydier, Fréderic; Simon, Arnauld; Beldjord, Kheïra; Reman, Oumédaly; Witz, Francis; Fagot, T.; Tavernier, Emmanuelle; Turlure, Pascal; Leguay, Thibaut; Huguet, Françoise; Vernant, Jean‐Paul; Daniel, F.; Béné, Marie‐Christine; Ifrah, Norbert; Thomas, Xavier; Dombret, Hervé; Macintyre, Elizabeth

doi:10.1182/blood-2008-10-184069

Cited by 202 publications

(171 citation statements)

References 39 publications

Supporting

Mentioning

153

Contrasting

Unclassified

Order By: Relevance

“…In contrast, the incidence of NOTCH1/FBXW7 mutations (47%) was lower in refractory/relapsed T-ALL than in the general unselected T-ALL population and these mutations were mostly found in combination with a second lesion in the pathway or different pathways, in line with their association with a favorable prognosis. [30][31][32][33] Moreover, we observed that NOTCH1/FBXW7 status could differ between matched diagnostic and relapse samples, indicating that NOTCH1/FBXW7 mutations might be secondary events in T-ALL.…”

Section: Discussionmentioning

confidence: 85%

RNA sequencing unravels the genetics of refractory/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications

et al. 2016

View full text Add to dashboard Cite

Despite therapeutic improvements, a sizable number of patients with T-cell acute lymphoblastic leukemia still have a poor outcome. To unravel the genomic background associated with refractoriness, we evaluated the transcriptome of 19 cases of refractory/early relapsed T-cell acute lymphoblastic leukemia (discovery cohort) by performing RNA-sequencing on diagnostic material. The incidence and prognostic impact of the most frequently mutated pathways were validated by Sanger sequencing on genomic DNA from diagnostic samples of an independent cohort of 49 cases (validation cohort), including refractory, relapsed and responsive cases. Combined gene expression and fusion transcript analyses in the discovery cohort revealed the presence of known oncogenes and identified novel rearrangements inducing overexpression, as well as inactivation of tumor suppressor genes. Mutation analysis identified JAK/STAT and RAS/PTEN as the most commonly disrupted pathways in patients with chemorefractory disease or early relapse, frequently in association with NOTCH1/FBXW7 mutations. The analysis on the validation cohort documented a significantly higher risk of relapse, inferior overall survival, disease-free survival and event-free survival in patients with JAK/STAT or RAS/PTEN alterations. Conversely, a significantly better survival was observed in patients harboring only NOTCH1/FBXW7 mutations: this favorable prognostic effect was abrogated by the presence of concomitant mutations. Preliminary in vitro assays on primary cells demonstrated sensitivity to specific inhibitors. These data document the negative prognostic impact of JAK/STAT and RAS/PTEN mutations in T-cell acute lymphoblastic leukemia and suggest the potential clinical application of JAK and PI3K/mTOR inhibitors in patients harboring mutations in these pathways.

show abstract

Section: Discussionmentioning

confidence: 85%

RNA sequencing unravels the genetics of refractory/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Thus, analysis of 141 T-ALLs treated in the Lymphoblastic Acute Leukemia in Adults (LALA)-94 (n ¼ 87) and the GRAALL-2003 (n ¼ 54) trials showed positive prognosis for patients with NOTCH1 and/or FBXW7 mutations. 9 Yet, these results could not be validated in a series of 88 patients treated in the MRC UKALLXII/ECOGE2993 protocol. 10 Overall these studies suggested that NOTCH1 mutations could be associated with improved outcome in some series, but that the prognostic impact of NOTCH1 mutations in T-ALL could be influenced by differences in therapy.…”

mentioning

confidence: 97%

NOTCH mutations as prognostic markers in T-ALL

Ferrando

2010

Leukemia

View full text Add to dashboard Cite

“…21,22 Among many other mutations in T-cell ALL, NOTCH1 or FBXW7 mutations are associated with a favorable prognosis, and NUP214-ABL1 fusion is responsive to tyrosine kinase inhibition. [23][24][25] Recent genome-wide studies in precursor B-cell ALL identified two high-risk subgroups, one with a genetic profile similar to that of cases with BCR-ABL1 fusion, characterized by IKZF1 deletion, and the other with a JAK2 mutation. 26 -28 These data suggest potential new therapeutic targets, including gamma secretase inhibitors, to target NOTCH1 mutations and JAK and ABL kinase inhibitors.…”

Section: Biological and Clinical Prognostic Factors In All: Setting Tmentioning

confidence: 99%

Adolescents and Young Adults with Acute Lymphoblastic Leukemia

Stock

2010

Hematology

106

View full text Add to dashboard Cite

During the last decade, increasing attention has been paid to a unique group of patients with acute lymphoblastic leukemia (ALL) who lie at the crossroad of therapeutic care by pediatric and adult hematologists/oncologists. ALL is a disease that affects infants, children, adolescents, and adult patients. With current therapies, the vast majority of children with ALL are now long-term survivors; unfortunately, the same good results have not yet been obtained for adults with ALL. This review will describe current controversies surrounding the treatment of adolescents and young adults with ALL-a group who finds themselves in the transition from "pediatric" to "adult" treatment approaches. The review focuses on recent insights into disease biology, prognostic factors, and treatment outcomes that have led to a series of prospective clinical trials specifically designed for adolescents and younger adults (AYAs) with ALL. These trials have been designed to provide important new clinical, psychosocial, and biological insights, and to further improve the survival of this challenging and unique group of patients.

show abstract

NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study

Abstract: Many somatic genetic abnormalities have been identified in T-cell acute lymphoblastic leukemia (T-ALL) but each individual

Cited by 202 publications

References 39 publications

RNA sequencing unravels the genetics of refractory/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications

RNA sequencing unravels the genetics of refractory/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications

NOTCH mutations as prognostic markers in T-ALL

Adolescents and Young Adults with Acute Lymphoblastic Leukemia

Contact Info

Product

Resources

About