Genetic rearrangements in relation to immunophenotype and outcome in T-cell acute lymphoblastic leukaemia

Meijerink, Jules P.P.

doi:10.1016/j.beha.2010.08.002

Cited by 86 publications

(49 citation statements)

References 105 publications

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“…Although there has been considerable investigation into genetic mechanisms of T-cell ALL (T-ALL) over the past decade, with the ability to identify nonoverlapping genetic subgroups of T-ALL that can, to some extent, be matched to stages of differentiation, 126 assays to measure these are not yet standard and the prognostic implications still controversial; thus, most differentiation stage subgroups are not formally included in the classification. However, 1 subset with unique biology is recognized as a new provisional entity (see next paragraph).…”

Section: T-cell Lymphoblastic Leukemia/lymphoma (T-all)mentioning

confidence: 99%

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

Arber

Orazi

Hasserjian

et al. 2016

Blood

8,287

7,810

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The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. Since then, there have been numerous advances in the identification of unique biomarkers associated with some myeloid neoplasms and acute leukemias, largely derived from gene expression analysis and next-generation sequencing that can significantly improve the diagnostic criteria as well as the prognostic relevance of entities currently included in the WHO classification and that also suggest new entities that should be added. Therefore, there is a clear need for a revision to the current classification. The revisions to the categories of myeloid neoplasms and acute leukemia will be published in a monograph in 2016 and reflect a consensus of opinion of hematopathologists, hematologists, oncologists, and geneticists. The 2016 edition represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition. The major changes in the classification and their rationale are presented here.

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Section: T-cell Lymphoblastic Leukemia/lymphoma (T-all)mentioning

confidence: 99%

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

Arber

Orazi

Hasserjian

et al. 2016

Blood

8,287

7,810

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“…1 T-cell transformation is characterized by aberrant expression of oncogenic transcription factors combined with inactivation of tumor suppressor genes (eg, phosphatase and tensin homolog [PTEN], CDKN2A) and/or activation of the NOTCH1 pathway. 2 The ectopic expression of oncogenes is typically caused by chromosomal rearrangements, the so-called type A hits, that place oncogenes under the control of T-cell-specific promoters or enhancer elements. 3,4 The analysis of translocation breakpoints revealed frequent involvement of illegitimate V(D)J recombination in these translocations by binding of recombination-activating gene 1/2 (RAG1/2) proteins to sequences that resemble authentic recombination signal sequences (RSSs).…”

Section: Introductionmentioning

confidence: 99%

“…5 These recurrent chromosomal rearrangements activate several oncogenes, such as TAL1, LMO2, TLX3, TLX1, or NKX2-1/ NKX2-2, which are believed to represent the clonal disease drivers. 2,6 Besides near mutually exclusive type A mutations, recurrent genetic aberrations that affect cell viability and/or proliferation, the so-called type B hits, are found in nearly all T-ALL genetic subgroups. Type B mutations include NOTCH1-activating mutations affecting NOTCH1 and FBXW7 that are found in over 60% of pediatric T-ALL patients [7][8][9][10][11] (reviewed in Ferrando 12 ), as well as less frequent events such as IL7R mutations in ;10% of T-ALL cases.…”

Section: Introductionmentioning

confidence: 99%

PTEN microdeletions in T-cell acute lymphoblastic leukemia are caused by illegitimate RAG-mediated recombination events

Mendes

Sarmento

Canté-Barrett

et al. 2014

Blood

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Key Points• Microdeletions represent an additional inactivation mechanism for PTEN in human T-cell acute lymphoblastic leukemia.• PTEN microdeletions are RAG-mediated aberrations.Phosphatase and tensin homolog (PTEN)-inactivating mutations and/or deletions are an independent risk factor for relapse of T-cell acute lymphoblastic leukemia (T-ALL) patients treated on Dutch Childhood Oncology Group or German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia protocols. Some monoallelic mutated or PTEN wild-type patients lack PTEN protein, implying that additional PTEN inactivation mechanisms exist. We show that PTEN is inactivated by small deletions affecting a few exons in 8% of pediatric T-ALL patients. These microdeletions were clonal in 3% and subclonal in 5% of patients. Conserved deletion breakpoints are flanked by cryptic recombination signal sequences (cRSSs) and frequently have non-template-derived nucleotides inserted in between breakpoints, pointing to an illegitimate RAG recombination-driven activity. Identified cRSSs drive RAG-dependent recombination in a reporter system as efficiently as bona fide RSSs that flank gene segments of the T-cell receptor locus. Remarkably, equivalent microdeletions were detected in thymocytes of healthy individuals. Microdeletions strongly associate with the TALLMO subtype characterized by TAL1 or LMO2 rearrangements. Primary and secondary xenotransplantation of TAL1-rearranged leukemia allowed development of leukemic subclones with newly acquired PTEN microdeletions. Ongoing RAG activity may therefore actively contribute to the acquisition of preleukemic hits, clonal diversification, and disease progression. (Blood. 2014;124(4):567-578)

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“…3 Developmental arrest seems dependent on the presence of so-called "type A mutations", which activate either T-ALL oncogenes such as TAL1, LMO2, TLX3, TLX1, NKX2-1/NKX2-2 or fusion proteins that activate HOXA genes. [4][5][6] For TLX oncoproteins, it has recently been found that these can directly interfere with TRA@ rearrangements by binding to ETS1 on the Eα enhancer resulting in a block of active transcription, histone modification-dependent chromatin opening and rearrangements resulting in a developmental arrest. 7 Various studies have identified T-ALL entities that arrest at an extremely immature developmental stage.…”

Section: Introductionmentioning

confidence: 99%

Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors

et al. 2013

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Genetic rearrangements in relation to immunophenotype and outcome in T-cell acute lymphoblastic leukaemia

Cited by 86 publications

References 105 publications

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia

PTEN microdeletions in T-cell acute lymphoblastic leukemia are caused by illegitimate RAG-mediated recombination events

Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors

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