2014
DOI: 10.1182/blood-2013-02-481507
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NOTCH2 and FLT3 gene mis-splicings are common events in patients with acute myeloid leukemia (AML): new potential targets in AML

Abstract: • Overall, our results suggest that NOTCH2 and FLT3 aberrant splicing is a common event in AML that correlates with disease status and may correlate with disease outcomes. • Selected variants of NOTCH2and FLT3 transcripts were detected in a significant number of AML patients and could be useful as disease markers.Our previous studies revealed an increase in alternative splicing of multiple RNAs in cells from patients with acute myeloid leukemia (AML) compared with CD34 1 bone marrow cells from normal donors. A… Show more

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Cited by 41 publications
(38 citation statements)
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References 38 publications
(55 reference statements)
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“…NOTCH2 and FLT3 aberrant splicing is observed in more than 70% of AML cases at diagnosis and their expressions decrease at remission. NOTCH-2Va and FLT3-Va transcripts are detected in a significant number of AML patients and high level of NOTCH-2Va predicts worse outcome independent of other known clinical indicators (75).…”
Section: Abnormally Spliced (As) Mrnas In Amlmentioning
confidence: 99%
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“…NOTCH2 and FLT3 aberrant splicing is observed in more than 70% of AML cases at diagnosis and their expressions decrease at remission. NOTCH-2Va and FLT3-Va transcripts are detected in a significant number of AML patients and high level of NOTCH-2Va predicts worse outcome independent of other known clinical indicators (75).…”
Section: Abnormally Spliced (As) Mrnas In Amlmentioning
confidence: 99%
“…Surprisingly, FLT3, together with NOTCH2 has been identified as the most commonly mis-spliced genes in more than 70% of AML patients (74). The splice variants of NOTCH2 and FLT3 are produced through complete or partial exon skipping and utilization of cryptic splice sites (75). NOTCH2 and FLT3 aberrant splicing is observed in more than 70% of AML cases at diagnosis and their expressions decrease at remission.…”
Section: Abnormally Spliced (As) Mrnas In Amlmentioning
confidence: 99%
See 1 more Smart Citation
“…Recent analysis of a large splicing array data set suggests that splicing signatures may be more effective than gene expression profiles for the characterization of cancers . Several unique mRNA isoforms have been linked to specific cancer types, including breast (Eswaran et al 2013), ovarian (Venables et al 2009), lung (Misquitta-Ali et al 2011), pancreatic (Omenn et al 2010), head and neck (Li et al 2014), digestive tract (Miura et al 2011), renal (Malouf et al 2014), gastric malignancies (Liu et al 2014), neuroblastoma (Chen et al 2015), and AML (Adamia et al 2014). These alternatively spliced transcripts, reflecting an independent layer and critical component of regulated gene expression, may thus serve as a new class of biomarkers.…”
Section: Introductionmentioning
confidence: 99%
“…128 Genome-wide analysis using exon arrays identified frequent alternative splicing of NOTCH2 in AML. 129 July 2012). This RBP-Jk variant is unable to form a complex with NOTCH proteins, cannot bind canonical RBP-Jk transcriptional sequences, and cannot rescue the distinct vessel phenotype induced by depletion of endogenous csl in a zebrafish model, indicating that the latter is a loss-of-function variant and supporting a tumorsuppressor function for the Notch pathway in the majority of AML patients (Figure 3).…”
Section: Mechanisms Of Notch Silencing In Amlmentioning
confidence: 99%