Detection of TEL-AML1/TEL-ABL fusion genes using a multi-fusion gene QRT-PCR screening method in acute lymphoblastic leukemia

2016 ◽  
Vol 44 (9) ◽  
pp. S88
Author(s):  
Yufeng Liu ◽  
Jingyu Zhang ◽  
Shuting Mao ◽  
Shufang Su ◽  
Linlin Wei
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Screening Method ◽  
Fusion Genes ◽  
Pcr Screening ◽  
Qrt Pcr

scholarly journals Identification and Characterization of Novel Fusion Genes with Potential Clinical Applications in Mexican Children with Acute Lymphoblastic Leukemia

2019 ◽  
Vol 20 (10) ◽  
pp. 2394 ◽  
Author(s):  
Minerva Mata-Rocha ◽  
Angelica Rangel-López ◽  
Elva Jiménez-Hernández ◽  
Blanca Angélica Morales-Castillo ◽  
Carolina González-Torres ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Fusion Genes ◽  
Cancer Etiology ◽  
Mexican Children ◽  
Genes Encoding ◽  
Identification And Characterization ◽  
Current Risk

Acute lymphoblastic leukemia is the most common type of childhood cancer worldwide. Mexico City has one of the highest incidences and mortality rates of this cancer. It has previously been recognized that chromosomal translocations are important in cancer etiology. Specific fusion genes have been considered as important treatment targets in childhood acute lymphoblastic leukemia (ALL). The present research aimed at the identification and characterization of novel fusion genes with potential clinical implications in Mexican children with acute lymphoblastic leukemia. The RNA-sequencing approach was used. Four fusion genes not previously reported were identified: CREBBP-SRGAP2B, DNAH14-IKZF1, ETV6-SNUPN, ETV6-NUFIP1. Although a fusion gene is not sufficient to cause leukemia, it could be involved in the pathogenesis of the disease. Notably, these new translocations were found in genes encoding for hematopoietic transcription factors which are known to play an important role in leukemogenesis and disease prognosis such as IKZF1, CREBBP, and ETV6. In addition, they may have an impact on the prognosis of Mexican pediatric patients with ALL, with the potential to be included in the current risk stratification schemes or used as therapeutic targets.

The Heterogeneous Fusion Gene Landscape in Pediatric Acute Lymphoblastic Leukemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4081-4081
Author(s):  
Yanara Marincevic-Zuniga ◽  
Johan Dahlberg ◽  
Sara Nilsson ◽  
Amanda Raine ◽  
Jonas Abrahamsson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Acute Lymphoblastic Leukemia ◽  
Gene Fusion ◽  
Conflicts Of Interest ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Fusion Genes ◽  
Fusion Transcripts ◽  
Pediatric All

Abstract Background: Next generation sequencing allows for the detection of expressed fusion transcripts across the transcriptome and has spurred the discovery of many novel chimeric transcripts in various cancers. Structural chromosomal rearrangements that lead to fusion transcripts are a hallmark of acute lymphoblastic leukemia (ALL) and serve as markers for diagnosis and stratification of pediatric ALL patients into prognostically relevant subgroups. Improved delineation of structural alterations in ALL could provide additional information for prognosis in ALL and for improved stratification of patients into treatment groups. Methods: To identify novel fusion transcripts in primary pediatric ALL cells we performed whole transcriptome sequencing of 134 BCP and T-ALL patient samples collected at diagnosis. Our study include samples from patients with the well-known ALL subtypes t(12;21)ETV6-RUNX1, high hyperdiploid (51-67 chromosomes), t(9;22)BCR-ABL1, 11q23/MLL and dic(9;20), in addition to patients with undefined karyotype or non-recurrent cytogenetic aberrations ("undefined" and "other") (n=58). FusionCatcher was used for the detection of somatic fusion genes, followed by a stringent filtering pipeline including gene fusion validation by Sanger sequencing in order to reduce the number of false positives. Principal component analysis (PCA) of patients with fusion genes was performed using genome wide gene expression levels and DNA methylation levels (Infinium HumanMethylation450 bead array). Results: We identified and validated 60 unique fusion events in almost half of the analyzed patients (n=69). Of the identified fusion genes, 60% have not previously been reported in ALL or other forms of cancer. The majority of the fusion genes were found in a single patient, but 23% were recurrent, including known ALL fusion genes (n=10) and novel fusion genes (n=7). We found that BCP-ALL samples displayed a higher number of validated fusion genes (54%) compared to the T-ALL samples (28%) moreover in BCP-ALL patients with "other" and "undefined" karyotypes, we detected fusion genes in 71% and 61% of the samples, respectively. High hyperdiploid patients had the lowest rate of validated fusion genes (24%) compared to the other well-known subtypes, where we detected subtype-associated fusion genes in 97% of cases. We also identified promiscuous fusion gene partners, such as ETV6, RUNX1, PAX5 and ZNF384 that fused with up to five different genes. Interestingly, PCA revealed molecularly distinct gene expression and DNA methylation signatures associated with these fusion partners. Conclusion: RNA-sequencing of pediatric ALL cells revealed a detailed view of the heterogeneous fusion gene landscape, identifying both known and novel fusion genes. By grouping samples based on recurrent gene fusion partners we are able to find shared gene expression and DNA methylation patterns compared to other subtypes of ALL, suggesting a shared molecular etiology within these distinct subgroups, offering novel insights into the delineation of fusion genes in ALL. Disclosures No relevant conflicts of interest to declare.

Targeting Kinase-activating Genetic Lesions to Improve Therapy of Pediatric Acute Lymphoblastic Leukemia

2018 ◽  
Vol 25 (24) ◽  
pp. 2811-2825 ◽  
Author(s):  
Raffaella Franca ◽  
Natasa K. Kuzelicki ◽  
Claudio Sorio ◽  
Eleonora Toffoletti ◽  
Oksana Montecchini ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Fusion Gene ◽  
Hematologic Malignancy ◽  
Lymphoblastic Leukemia ◽  
Point Of View ◽  
Lymphoid Cells ◽  
Gene Encoding ◽  
Pediatric All ◽  
Blast Cells ◽  
Tk Inhibitors

Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children, characterized by an abnormal proliferation of immature lymphoid cells. Thanks to risk-adapted combination chemotherapy treatments currently used, survival at 5 years has reached 90%. ALL is a heterogeneous disease from a genetic point of view: patients’ lymphoblasts may harbor in fact several chromosomal alterations, some of which have prognostic and therapeutic value. Of particular importance is the translocation t(9;22)(q34;q11.2) that leads to the formation of the BCR-ABL1 fusion gene, encoding a constitutively active chimeric tyrosine kinase (TK): BCR-ABL1 that is present in ~3% of pediatric ALL patients with B-immunophenotype and is associated with a poor outcome. This type of ALL is potentially treatable with specific TK inhibitors, such as imatinib. Recent studies have demonstrated the existence of a subset of BCR-ABL1 like leukemias (~10-15% of Bimmunophenotype ALL), whose blast cells have a gene expression profile similar to that of BCR-ABL1 despite the absence of t(9;22)(q34;q11.2). The precise pathogenesis of BCR-ABL1 like ALL is still to be defined, but they are mainly characterized by the activation of constitutive signal transduction pathways due to chimeric TKs different from BCR-ABL1. BCR-ABL1 like ALL patients represent a group with unfavorable outcome and are not identified by current risk criteria. In this review, we will discuss the design of targeted therapy for patients with BCR-ABL1 like ALL, which could consider TK inhibitors, and discuss innovative approaches suitable to identify the presence of patient’s specific chimeric TK fusion genes, such as targeted locus amplification or proteomic biosensors.

Occurrence of anMLL/LAF4 fusion gene caused by the insertion ins(11;2)(q23;q11.2q11.2) in an infant with acute lymphoblastic leukemia

2003 ◽  
Vol 37 (1) ◽  
pp. 106-109 ◽  
Author(s):  
Jochen Bruch ◽  
Monika Wilda ◽  
Andrea Teigler-Schlegel ◽  
Jochen Harbott ◽  
Arndt Borkhardt ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia

scholarly journals Heterogeneous patterns of amplification of the NUP214-ABL1 fusion gene in T-cell acute lymphoblastic leukemia

Leukemia ◽  
2008 ◽  
Vol 23 (1) ◽  
pp. 125-133 ◽  
Author(s):  
C Graux ◽  
◽  
M Stevens-Kroef ◽  
M Lafage ◽  
N Dastugue ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals NUTM1 is a recurrent fusion gene partner in B-cell precursor acute lymphoblastic leukemia associated with increased expression of genes on chromosome band 10p12.31-12.2

Haematologica ◽  
2019 ◽  
Vol 104 (10) ◽  
pp. e455-e459 ◽  
Author(s):  
Femke M. Hormann ◽  
Alex Q. Hoogkamer ◽  
H. Berna Beverloo ◽  
Aurélie Boeree ◽  
Ilse Dingjan ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Chromosome Band ◽  
Cell Precursor ◽  
Expression Of Genes
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