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

Jess F. Peterson, Beth A. Pitel, Stephanie A. Smoley, James Smadbeck, Sarah H. Johnson, George Vasmatzis, Sarah J. Koon, Matthew R. Webley, Mary McGrath, Michael G. Bayerl, Linda Baughn, Ross A. Rowsey, Rhett P. Ketterling, Patricia T Greipp, Nicole L. Hoppman

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalCold Spring Harbor molecular case studies
Volume5
Issue number2
DOIs
StatePublished - Apr 1 2019

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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Pediatrics
T-cells
Gene Fusion
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Fusion reactions
Genes
Protein-Tyrosine Kinases
Technology
Hematologic Neoplasms
Fluorescence In Situ Hybridization
Cytogenetics
Chromosome Aberrations
Bone
Blood
Color
Bone Marrow
Fluorescence
Genome
Therapeutics

Keywords

  • T-cell acute lymphoblastic leukemias

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Detection of a cryptic NUP214/ABL1 gene fusion by mate-pair sequencing (MPseq) in a newly diagnosed case of pediatric T-lymphoblastic leukemia. / Peterson, Jess F.; Pitel, Beth A.; Smoley, Stephanie A.; Smadbeck, James; Johnson, Sarah H.; Vasmatzis, George; Koon, Sarah J.; Webley, Matthew R.; McGrath, Mary; Bayerl, Michael G.; Baughn, Linda; Rowsey, Ross A.; Ketterling, Rhett P.; Greipp, Patricia T; Hoppman, Nicole L.

In: Cold Spring Harbor molecular case studies, Vol. 5, No. 2, 01.04.2019.

Research output: Contribution to journalArticle

Peterson, Jess F. ; Pitel, Beth A. ; Smoley, Stephanie A. ; Smadbeck, James ; Johnson, Sarah H. ; Vasmatzis, George ; Koon, Sarah J. ; Webley, Matthew R. ; McGrath, Mary ; Bayerl, Michael G. ; Baughn, Linda ; Rowsey, Ross A. ; Ketterling, Rhett P. ; Greipp, Patricia T ; Hoppman, Nicole L. / Detection of a cryptic NUP214/ABL1 gene fusion by mate-pair sequencing (MPseq) in a newly diagnosed case of pediatric T-lymphoblastic leukemia. In: Cold Spring Harbor molecular case studies. 2019 ; Vol. 5, No. 2.
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AU - Bayerl, Michael G.

AU - Baughn, Linda

AU - Rowsey, Ross A.

AU - Ketterling, Rhett P.

AU - Greipp, Patricia T

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