Acute promyelocytic leukemia with a cryptic insertion of RARA into TBL1XR1.
Child, Preschool
Female
Gene Fusion
/ genetics
Humans
INDEL Mutation
/ genetics
Karyotype
Karyotyping
Leukemia, Promyelocytic, Acute
/ genetics
Promyelocytic Leukemia Protein
/ genetics
Receptors, Cytoplasmic and Nuclear
/ genetics
Repressor Proteins
/ genetics
Retinoic Acid Receptor alpha
/ genetics
Translocation, Genetic
/ genetics
Whole Genome Sequencing
TBL1XR1/RARA
acute promyelocytic leukemia
children
cryptic insertion
Journal
Genes, chromosomes & cancer
ISSN: 1098-2264
Titre abrégé: Genes Chromosomes Cancer
Pays: United States
ID NLM: 9007329
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
21
05
2019
revised:
10
07
2019
accepted:
11
07
2019
pubmed:
28
7
2019
medline:
15
2
2020
entrez:
28
7
2019
Statut:
ppublish
Résumé
Acute promyelocytic leukemia (APL) is cytogenetically characterized by the t(15;17) (q24;q21), although cases without this translocation exist. These cases are referred to as "cryptic" or "masked" translocations. Additionally, fewer than 5% of APL cases have another partner gene fused to the RARA gene. The TBL1XR1-RARA fusion gene has recently been reported as a novel RARA-associated fusion gene. We report a case with TBL1XR1-RARA and a masked translocation that was not detected by conventional tests for RARA-associated translocations. Three-year-old girl was diagnosed with APL based morphological findings, although conventional tests for RARA-associated chimeric genes were negative. She received all-trans retinoic acid treatment, but that was not effective. She achieved a complete remission (CR) by conventional multidrug chemotherapy, but had extramedullary relapse 2 years after onset. She underwent cord blood transplantation (CBT) in her second CR and is currently alive. To investigate the underlying pathogenesis of this unique case, we performed whole-genome sequencing and found a cryptic insertion of RARA gene into the TBL1XR1 gene. The transcript of the chimeric gene, TBL1XR1-RARA, was confirmed as an in-frame fusion by RT-PCR. In conclusion, we found using next-generation sequencing (NGS) a TBL1XR1-RARA fusion in a child with variant APL without the classic karyotype. Cryptic insertion could also occur in cases other than APL with PML-RARA. Variant APL has many variants and NGS analysis should therefore be considered for APL variant cases, even for those without RARA translocation detected by conventional analysis.
Substances chimiques
Promyelocytic Leukemia Protein
0
RARA protein, human
0
Receptors, Cytoplasmic and Nuclear
0
Repressor Proteins
0
Retinoic Acid Receptor alpha
0
TBL1XR1 protein, human
0
PML protein, human
143220-95-5
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
820-823Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
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