Clinical and genomic characterization of an ATRA-insensitive acute promyelocytic leukemia variant with a FNDC3B::RARB fusion

被引：5

作者：

Kirkham, Justin K. ^{[1
]}

Liu, Yen-Chun ^{[2
]}

Foy, Scott G. ^{[3
]}

Ma, Jing ^{[2
]}

Gheorghe, Gabriela ^{[2
]}

Furtado, Larissa V. ^{[2
]}

Popescu, Marcela I. ^{[4
]}

Klco, Jeffery M. ^{[2
]}

Karol, Seth E. ^{[1
]}

Blackburn, Patrick R. ^{[2
,5
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN USA

[2] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN USA

[3] St Jude Childrens Res Hosp, Dept Computat Biol, Memphis, TN USA

[4] East Tennessee State Univ, James H Quillen Coll Med, Dept Pediat Hematol & Oncol, Johnson City, TN USA

[5] St Jude Childrens Res Hosp, Dept Pathol, 262 Danny Thomas Pl, Memphis, TN 38105 USA

来源：

GENES CHROMOSOMES & CANCER | 2023年 / 62卷 / 10期

关键词：

acute promyelocytic leukemia (APL); all-trans-retinoic acid (ATRA); exome sequencing; FNDC3B; RARB; genome sequencing; RNA-sequencing;

D O I：

10.1002/gcc.23180

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The promyelocytic leukemia-retinoic acid receptor-alpha (PML::RARA) fusion is the hallmark of acute promyelocytic leukemia (APL) and is observed in over 95% of APL cases. RARA and homologous receptors RARB and RARG are occasionally fused to other gene partners, which differentially affect sensitivity to targeted therapies. Most APLs without RARA fusions have rearrangements involving RARG or RARB, both of which frequently show resistance to all-trans-retinoic acid (ATRA) and/or multiagent chemotherapy for acute myeloid leukemia (AML). We present a 13-year-old male diagnosed with variant APL with a novel FNDC3B::RARB in-frame fusion that showed no response to ATRA but responded well to conventional AML therapy. While FNDC3B has been identified as a rare RARA translocation partner in ATRA-sensitive variant APL, it has never been reported as a fusion partner with RARB and it is only the second known fusion partner with RARB in variant APL. We also show that this novel fusion confers an RNA expression signature that is similar to APL, despite clinical resistance to ATRA monotherapy.

引用

页码：617 / 623

页数：7

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