Prognostic implications of mutations in <i>NOTCH1</i>
 and <i>FBXW7</i>
 in childhood T-all treated according to the NOPHO ALL-1992 and ALL-2000 protocols

Fogelstrand, Linda; Staffas, Anna; Wasslavik, Carina; Sjögren, Helene; Söderhäll, Stefan; Frost, Britt‐Marie; Forestier, Erik; Degerman, Sofie; Behrendtz, Mikael; Heldrup, Jesper; Karrman, Kristina; Johansson, Bertil; Heyman, Mats; Abrahamsson, Jonas; Palmqvist, Lars

doi:10.1002/pbc.24803

Cited by 31 publications

(25 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar observations have also been made in T-ALL (10). Conversely, patients with T-LBL and loss of heterozygosity of 6q14-24 have a poor prognosis and an increased risk of relapse (2).…”

Section: Discussionsupporting

confidence: 79%

Primary orbital precursor T-cell lymphoblastic lymphoma: Report of a unique case

Stenman

Persson

Enlund

et al. 2016

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. Primary T-cell lymphoblastic lymphoma (T-LBL)in the eye region is very rare. The present study described a unique case of T-LBL involving the extraocular muscles. A 22-year-old male patient presented with a 3-week history of headache, reduced visual acuity and edema of the left eye. Clinical examination revealed left-sided exophthalmus, periorbital edema, chemosis, and reduced motility of the left eye. A magnetic resonance imaging scan revealed thickening of the left orbital muscles and a positron emission tomoga positron emission tomography-computed tomography scan also demonstrated activity in a subclavicular lymph node. Histopathological analysis of both lesions revealed infiltration by medium-sized neoplastic lymphoid cells with a high nuclear-cytoplasmic ratio and a high mitotic index. Immunostaining revealed positivity for CD2, CD3, CD99, Tia-1, and GranzymB, and variable positivity for CD4. There was no involvement of the bone marrow. Based on the clinical and histopathological findings, a diagnosis of T-LBL was made. There was no evidence of NOTCH1 mutation or rearrangements of the ETV6 and MLL genes and high-resolution array-based comparative genomic hybridization (arrayCGH) analysis revealed a normal genomic profile. The patient received chemotherapy according to the high-risk NOPHO protocol, followed by myeloablative allogenic bone marrow transplantation. At 35 months after diagnosis, the patient remained in complete first remission, but without light perception on his left eye. To the best of our knowledge, this is the first report of a case of T-LBL involving the extraocular muscles. Although primary T-LBL in the eye region is very rare, our findings demonstrate that lymphoma should be considered in the differential diagnosis of patients with similar symptoms.

show abstract

“…Similar observations have also been made in T-ALL (10). Conversely, patients with T-LBL and loss of heterozygosity of 6q14-24 have a poor prognosis and an increased risk of relapse (2).…”

Section: Discussionsupporting

confidence: 79%

Primary orbital precursor T-cell lymphoblastic lymphoma: Report of a unique case

Stenman

Persson

Enlund

et al. 2016

Molecular and Clinical Oncology

View full text Add to dashboard Cite

show abstract

“…This could of course reflect differences in therapy among treatment protocols. Jenkinson et al () reported a significantly improved overall survival of pediatric T‐ALL cases with coexisting FBXW7 and NOTCH1 mutations, but that could not be confirmed in a Swedish T‐ALL cohort (Fogelstrand et al, ). Finally, a meta‐analysis of 711 pediatric T‐ALL patients did not find any correlation between the presence of NOTCH1 mutations and event‐free survival (Ma and Wu, ).…”

Section: Clinical Genetic and Epigenetic Features And Prognosismentioning

confidence: 99%

Pediatric T‐cell acute lymphoblastic leukemia

Karrman

Johansson

2016

Genes Chromosomes & Cancer

Self Cite

103

111

View full text Add to dashboard Cite

The most common pediatric malignancy is acute lymphoblastic leukemia (ALL), of which T‐cell ALL (T‐ALL) comprises 10–15% of cases. T‐ALL arises in the thymus from an immature thymocyte as a consequence of a stepwise accumulation of genetic and epigenetic aberrations. Crucial biological processes, such as differentiation, self‐renewal capacity, proliferation, and apoptosis, are targeted and deranged by several types of neoplasia‐associated genetic alteration, for example, translocations, deletions, and mutations of genes that code for proteins involved in signaling transduction, epigenetic regulation, and transcription. Epigenetically, T‐ALL is characterized by gene expression changes caused by hypermethylation of tumor suppressor genes, histone modifications, and miRNA and lncRNA abnormalities. Although some genetic and gene expression patterns have been associated with certain clinical features, such as immunophenotypic subtype and outcome, none has of yet generally been implemented in clinical routine for treatment decisions. The recent advent of massive parallel sequencing technologies has dramatically increased our knowledge of the genetic blueprint of T‐ALL, revealing numerous fusion genes as well as novel gene mutations. The challenges now are to integrate all genetic and epigenetic data into a coherent understanding of the pathogenesis of T‐ALL and to translate the wealth of information gained in the last few years into clinical use in the form of improved risk stratification and targeted therapies. Here, we provide an overview of pediatric T‐ALL with an emphasis on the acquired genetic alterations that result in this disease. © 2016 Wiley Periodicals, Inc.

show abstract

“…Ideally, biomarkers indicative of Notch-pathway activity with functional relevance in a specific tumour would guide patient stratification (that is, biomarkers predictive of response), but attempts to identify candidates for Notch-targeted therapy based on this premise have not proved straightforward. Expression levels of canonical Notch target genes is correlated with Notch-activating mutations and is a good indicator of Notch-pathway activity in T-cell acute lymphoblastic leukaemia (T-ALL); 62,63 however, this relationship does necessarily imply that expression of the same target genes is indicative of Notch activity in all malignancies owing to a number of factors—not least the notorious context-dependence of Notch signalling cascade and outcomes, which are dynamic and influenced by other chromatin cofactors. 64 Moreover, expression of different Notch paralogues varies across tumours.…”

Section: Targeting the Notch Pathwaymentioning

confidence: 99%

Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update

et al. 2015

View full text Add to dashboard Cite

During the past decade, cancer stem cells (CSCs) have been increasingly identified in many malignancies. Although the origin and plasticity of these cells remain controversial, tumour heterogeneity and the presence of small populations of cells with stem-like characteristics is established in most malignancies. CSCs display many features of embryonic or tissue stem cells, and typically demonstrate persistent activation of one or more highly conserved signal transduction pathways involved in development and tissue homeostasis, including the Notch, Hedgehog (HH), and Wnt pathways. CSCs generally have slow growth rates and are resistant to chemotherapy and/or radiotherapy. Thus, new treatment strategies targeting these pathways to control stem-cell replication, survival and differentiation are under development. Herein, we provide an update on the latest advances in the clinical development of such approaches, and discuss strategies for overcoming CSC-associated primary or acquired resistance to cancer treatment. Given the crosstalk between the different embryonic developmental signalling pathways, as well as other pathways, designing clinical trials that target CSCs with rational combinations of agents to inhibit possible compensatory escape mechanisms could be of particular importance. We also share our views on the future directions for targeting CSCs to advance the clinical development of these classes of agents.

show abstract

Prognostic implications of mutations in NOTCH1 and FBXW7 in childhood T-all treated according to the NOPHO ALL-1992 and ALL-2000 protocols

Abstract: Increased NOTCH activity, reflected by increased HES1 expression, is associated with improved outcome in pediatric T-ALL, but its role as a diagnostic tool or a therapeutic target in future clinical treatment protocols remains to be elucidated.

Cited by 31 publications

References 37 publications

Primary orbital precursor T-cell lymphoblastic lymphoma: Report of a unique case

Primary orbital precursor T-cell lymphoblastic lymphoma: Report of a unique case

Pediatric T‐cell acute lymphoblastic leukemia

Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update

Contact Info

Product

Resources

About