<i>NUP214-ABL1</i>
            fusion defines a rare subtype of B-cell precursor acute lymphoblastic leukemia that could benefit from tyrosine kinase inhibitors

Duployez, Nicolas; Grzych, Guillaume; Ducourneau, Benoît; Fuentes, Martin Alarcon; Grardel, Nathalie; Boyer, Thomas D.; Chahla, Wadih Abou; Bruno, Bénédicte; Nelken, Brigitte; Clappier, Emmanuelle; Preudhomme, Claude

doi:10.3324/haematol.2015.136499

Cited by 36 publications

(31 citation statements)

References 10 publications

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“…Sensitivity tests performed in vitro and in patient-derived xenografts provided a solid rationale for prospective clinical testing of TKIs in BCP-ALL with novel kinase-activating aberrations 17 , 53 . However, a relatively limited number of such children already treated by TKIs have been reported in the literature so far 10 , 14 , 65 – 73 . Although several case reports described good response to ABL class inhibitors in patients with ABL1 / ABL2 or PDGFRB gene-involving fusions 10 , 66 , 67 , 70 – 72 , 74 and overall results are generally encouraging, in some patients the TKI-involving treatment failed to induce long-term remission.…”

Section: New Therapeutically Relevant Aberrations/categoriesmentioning

confidence: 99%

New biological and genetic classification and therapeutically relevant categories in childhood B-cell precursor acute lymphoblastic leukemia

2018

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Traditionally, genetic abnormalities detected by conventional karyotyping, fluorescence in situ hybridization, and polymerase chain reaction divided childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) into well-established genetic subtypes. This genetic classification has been prognostically relevant and thus used for the risk stratification of therapy. Recently, the introduction of genome-wide approaches, including massive parallel sequencing methods (whole-genome, -exome, and -transcriptome sequencing), enabled extensive genomic studies which, together with gene expression profiling, largely expanded our understanding of leukemia pathogenesis and its heterogeneity. Novel BCP-ALL subtypes have been described. Exact identification of recurrent genetic alterations and their combinations facilitates more precise risk stratification of patients. Discovery of targetable lesions in subsets of patients enables the introduction of new treatment modalities into clinical practice and stimulates the transfer of modern methods from research laboratories to routine practice.

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Section: New Therapeutically Relevant Aberrations/categoriesmentioning

confidence: 99%

New biological and genetic classification and therapeutically relevant categories in childhood B-cell precursor acute lymphoblastic leukemia

2018

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“…Although recurrent genetic abnormalities in many hematologic neoplasms add diagnostic, prognostic, and therapy-related value, the clinical significance of the known recurrent genetic abnormalities observed in T-ALL are mostly unclear or controversial (Borowitz et al 2017; Taylor et al 2017). Interestingly, the detection of ABL1 gene rearrangements, which are often associated with BCR/ABL1 -positive B-ALL and BCR-ABL1 -like (Ph-like) B-ALL (Pui et al 2017; Tasian et al 2017), have also been described in T-ALL—namely, NUP214 / ABL1 —and may be amenable to tyrosine kinase inhibitor (TKI) therapy (Graux et al 2004; Burmeister et al 2006; Quintás-Cardama et al 2008; Deenik et al 2009; Graux et al 2009; Hagemeijer and Graux 2010; Clarke et al 2011; De Braekeleer et al 2011; Duployez et al 2016; Simioni et al 2016; Chen et al 2017; Liu et al 2017). Considering the limited treatment options and overall unfavorable prognosis of T-ALL, detecting genetic abnormalities that may respond to targeted therapy is critical.…”

Section: Introductionmentioning

confidence: 99%

Detection of a cryptic NUP214/ABL1 gene fusion by mate-pair sequencing (MPseq) in a newly diagnosed case of pediatric T-lymphoblastic leukemia

Peterson

Pitel

Smoley

et al. 2019

Cold Spring Harb Mol Case Stud

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T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematopoietic neoplasm involving the bone marrow and blood that accounts for ∼15% of childhood and 25% of adult ALL. Whereas multiple, recurrent genetic abnormalities have been described in T-ALL, their clinical significance is unclear or controversial. Importantly, ABL1 rearrangements, most commonly described in BCR/ABL1 -positive B-ALL and BCR-ABL1 -like B-ALL, have been observed in T-ALL and may respond to tyrosine kinase inhibitor (TKI) therapy. We describe a newly diagnosed case of pediatric T-ALL with a fluorescence in situ hybridization abnormality suggesting a partial ABL1 deletion by a BCR / ABL1 dual-color dual-fusion probe but that demonstrated a normal result using an ABL1 break-apart probe. Mate-pair sequencing (MPseq), a next-generation sequencing (NGS)-based technology utilized to detect copy number and structural abnormalities with high resolution and precision throughout the genome, was performed and revealed a NUP214 / ABL1 gene fusion that has been demonstrated to be sensitive to TKI therapy. This case demonstrates the power of MPseq to resolve chromosomal abnormalities unappreciable by traditional cytogenetic methodologies and highlights the clinical value of this novel NGS-based technology.

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“…NUP214‐ABL1 was previously reported in patients with ALL and found in approximately 6% of T‐cell ALL patients . Compared with BCR‐ABL1 , which has the same kinase domain, NUP214‐ABL1 fusion protein differs in many critical catalytic properties and is more sensitive to TKIs, demonstrating that different fusion partners of the same kinase can determine functional properties . However, similar to our patient with AML with BCL6 gene fusion, the fusion was reported only in patients with lymphoblastic leukemia, and the significance in pathogenesis of AML is unknown.…”

Section: Discussionmentioning

confidence: 54%

Detection of recurrent, rare, and novel gene fusions in patients with acute leukemia using next‐generation sequencing approaches

Kim

Lee

et al. 2020

Hematological Oncology

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Identification of gene fusion is an essential part in the management of patients with acute leukemia, not only for diagnosis but also in predicting the treatment outcome and selecting appropriate treatment. Adopting next-generation sequencing (NGS) technology for identification of gene fusion in patients with acute leukemia can be a good alternative to conventional tests. In the present study, the NGS RNA fusion gene panel test was applied to diagnostic samples of patients with acute leukemia to identify fusion genes more efficiently. Among 134 patients with acute leukemia, 53 gene fusions were detected in 52 patients. In addition to the recurrent gene fusions specified in the WHO diagnostic criteria, 11 rare or novel gene fusions were identified. Of those, two were gene fusions associated with Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL), two were novel gene fusions, three were gene fusions with novel partner genes, and six were rare gene fusions from previous reports. We confirmed the clinical utility of the NGS test in identifying clinically significant gene fusions such as gene fusions involving KMT2A that has a large number of partners. Notably, Ph-like ALL-associated gene fusions could be easily identified despite the wide variety of genes involved. The results from the present study may contribute toward a better understanding of the genomic landscape of acute leukemia as well as patient management. K E Y W O R D Sacute leukemia, next-generation sequencing, RNA gene fusion detection

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NUP214-ABL1 fusion defines a rare subtype of B-cell precursor acute lymphoblastic leukemia that could benefit from tyrosine kinase inhibitors

Cited by 36 publications

References 10 publications

New biological and genetic classification and therapeutically relevant categories in childhood B-cell precursor acute lymphoblastic leukemia

New biological and genetic classification and therapeutically relevant categories in childhood B-cell precursor acute lymphoblastic leukemia

Detection of a cryptic NUP214/ABL1 gene fusion by mate-pair sequencing (MPseq) in a newly diagnosed case of pediatric T-lymphoblastic leukemia

Detection of recurrent, rare, and novel gene fusions in patients with acute leukemia using next‐generation sequencing approaches

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