Mutations of the Notch1 gene in T-cell acute lymphoblastic leukemia: analysis in adults and children

Lee, Soo-Youn; Kumano, Keiki; Masuda, Shigeo; Hangaishi, Akira; Takita, Junko; Nakazaki, Kumi; Kurokawa, Mineo; Hayashi, Yasuhide; Ogawa, Seishi; Chiba, Shigeru

doi:10.1038/sj.leu.2403896

Cited by 57 publications

(42 citation statements)

References 8 publications

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“…Interestingly, these mutations were not associated with a particular subtype of T-ALL and occurred in all major subtypes of T-ALL, both in pediatric and adult patients. [100][101][102] Obviously, these findings have therapeutic implications, as g-secretase inhibitors could be used to treat T-ALL. However, given that Notch signaling also is implicated in many other developmental processes, including HSC self-renewal, such approaches need to be implemented with great caution.…”

Section: Notch In T-cell Leukemiamentioning

confidence: 99%

Notch and Wnt signaling in T-lymphocyte development and acute lymphoblastic leukemia

2006

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Many acute lymphoblastic leukemias can be considered as malignant counterparts of cells in the various stages of normal lymphoid development in bone marrow and thymus. T-cell development in the thymus is an ordered and tightly controlled process. Two evolutionary conserved signaling pathways, which were first discovered in Drosophila, control the earliest steps of T-cell development. These are the Notch and Wnt-signaling routes, which both are deregulated in several types of leukemias. In this review we discuss both pathways, with respect to their signaling mechanisms, functions during T-cell development and their roles in development of leukemias, especially T-cell acute lymphoblastic leukemia.

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Section: Notch In T-cell Leukemiamentioning

confidence: 99%

Notch and Wnt signaling in T-lymphocyte development and acute lymphoblastic leukemia

2006

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“…Ten of the observed mutations were not previously described. 23,33 Two NOTCH1 mutations (in exon 26 and exon 34) were simultaneously present in one patient (2738). This is of particular interest because mutations in cis may lead to an enhanced NOTCH1 activity 20-to 40-fold.…”

Section: Discussionmentioning

confidence: 99%

“…References. 23,33 MRLP41, SSNA1 and PHPT1. The 9q34 duplicated leukemic subclone was still present at relapse in four patients analyzed, indicating that the 9q34 may provide cellular resistance towards chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Ten out of 17 mutations were novel mutations, whereas seven were identical [4].isht(5;14)(q33;q32) 1179_R M 17, 9 46,XY,der(6)t(6;8)(q26;q24),del(8)(q24), del(9)(p21p21),der(9)del(9)(p21p21)add(9)(q11), del(11)(q21q23) [6]/46,idem,der(3;9)(p10;q10), der(6)t(3;6)(q29;p25),+del (9) 9q34 duplication in pediatric T-ALL P van Vlierberghe et al to mutations previously described. 23,33 A leucine to proline conversion was observed most frequently (five of 17 mutations (29%)) at residues 1586, 1594, 1601 and 1679. Deletion of (GTG) at residue 1579 was observed in two patient samples.…”

Section: Identification Of Novel Notch1 Mutations In Pediatric T-allmentioning

confidence: 99%

“…22 Other abnormalities also involving the 9q34 region in T-ALL involve mutations in the NOTCH1 gene. [23][24][25][26][27][28][29][30][31][32][33] A role for NOTCH1 in human T-ALL was previously postulated due to its involvement in the rare chromosomal translocation t(7;9)(q34;q34.3). 24 The identification of activating NOTCH1 mutations in more than 50% of human T-ALL samples, 23 suggests a much broader role for this gene in human T-cell leukemogenesis.…”

Section: Introductionmentioning

confidence: 99%

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A new recurrent 9q34 duplication in pediatric T-cell acute lymphoblastic leukemia

et al. 2006

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Over the last decade, genetic characterization of T-cell acute lymphoblastic leukemia (T-ALL) has led to the identification of a variety of chromosomal abnormalities. In this study, we used array-comparative genome hybridization (array-CGH) and identified a novel recurrent 9q34 amplification in 33% (12/36) of pediatric T-ALL samples, which is therefore one of the most frequent cytogenetic abnormalities observed in T-ALL thus far. The exact size of the amplified region differed among patients, but the critical region encloses B4 Mb and includes NOTCH1. The 9q34 amplification may lead to elevated expression of various genes, and MRLP41, SSNA1 and PHPT1 were found significantly expressed at higher levels. Fluorescence in situ hybridization (FISH) analysis revealed that this 9q34 amplification was in fact a 9q34 duplication on one chromosome and could be identified in 17-39 percent of leukemic cells at diagnosis. Although this leukemic subclone did not predict for poor outcome, leukemic cells carrying this duplication were still present at relapse, indicating that these cells survived chemotherapeutic treatment. Episomal NUP214-ABL1 amplification and activating mutations in NOTCH1, two other recently identified 9q34 abnormalities in T-ALL, were also detected in our patient cohort. We showed that both of these genetic abnormalities occur independently from this newly identified 9q34 duplication.

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Frequent Mutations in TP53 and CDKN2A Found by Next-Generation Sequencing of Head and Neck Cancer Cell Lines

Nichols¹,

Yoo²,

Palma³

et al. 2012

Arch Otolaryngol Head Neck Surg

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Mutations of the Notch1 gene in T-cell acute lymphoblastic leukemia: analysis in adults and children

Cited by 57 publications

References 8 publications

Notch and Wnt signaling in T-lymphocyte development and acute lymphoblastic leukemia

Notch and Wnt signaling in T-lymphocyte development and acute lymphoblastic leukemia

A new recurrent 9q34 duplication in pediatric T-cell acute lymphoblastic leukemia

Frequent Mutations in TP53 and CDKN2A Found by Next-Generation Sequencing of Head and Neck Cancer Cell Lines

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