A novel entity of acute myeloid leukaemia with recurrent RARG-rearrangement resembling acute promyelocytic leukaemia

Luo, Hong; Suo, Zhiyong; Li, Ké; Chen, Xinghua; Li, Yanchun; Sun, Yuan; Liu, Lifeng; Yu, Huiyang; Zhu, Hong‐Hu

doi:10.1016/j.leukres.2018.12.009

Cited by 18 publications

(15 citation statements)

References 8 publications

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“…Additionally, RARB-related and RARG-related fusion genes have been reported in morphological APL cases recently. [12][13][14][15] As in our case, masked fusion genes could occur in variant APL cases. As conventional analysis alone will not detect all translocations of APL variants.…”

Section: Case Reportsupporting

confidence: 69%

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Acute promyelocytic leukemia with a cryptic insertion of RARA into TBL1XR1

Osumi

Watanabe

Okamura

et al. 2019

Genes Chromosomes & Cancer

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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.

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Section: Case Reportsupporting

confidence: 69%

“…[12][13][14][15] As in our case, masked fusion genes could occur in variant APL cases. Additionally, RARB-related and RARG-related fusion genes have been reported in morphological APL cases recently.…”

Section: Case Reportmentioning

confidence: 86%

Acute promyelocytic leukemia with a cryptic insertion of RARA into TBL1XR1

Osumi

Watanabe

Okamura

et al. 2019

Genes Chromosomes & Cancer

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“…[ 8 9 ] In our case, similar to the more recently reported case with the PML/RARG and NUP98/RARG fusion gene, the sensitivity to ATRA treatment was not established due to the early discontinuation of ATRA therapy. [5] Among the 7 patients who were reported with the RARG rearrangement,[ 3 10 11 ] none showed clear sensitivity to ATRA. But we can confirm the resistance to ATO in this NUP98/RARG fusion gene-positive AML patient, similar to other reports.…”

Section: Discussionmentioning

confidence: 99%

Alkaloid-based regimen is beneficial for acute myeloid leukemia resembling acute promyelocytic leukemia with NUP98/RARG fusion and RUNX1 mutation

et al. 2020

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Rationale: Some acute myeloid leukemia (AML) patients present with features mimicking the classical hypergranular subtype of acute promyelocytic leukemia (APL) but without the typical promyelocytic leukemia/retinoic acid receptor α (PML/RARα) rearrangement. Herein, we report an AML patient resembling APL but with nucleoporin 98/retinoid acid receptor gamma gene (NUP98/RARG) fusion transcript and Runt-related transcription factor 1 (RUNX1) mutation. Patient concerns: An 18-year-old male presented at the hospital with a diagnosis of AML. Diagnoses: The patient was diagnosed with bone marrow examination. Bone marrow smear displayed 90.5% promyelocytes. Fluorescence in situ hybridization analysis failed to detect the PML/RARα fusion transcript or RARα amplification. While real-time polymerase chain reaction showed positivity for the NUP98/RARG fusion transcript. G-banding karyotype analysis showed a normal karyotype. Interventions: The patient showed resistance to arsenic trioxide and standard 3 + 7 chemotherapy, but eventually achieved complete remission through the Homoharringtonine, Cytarabine, and Aclarubicin chemotherapy. Outcomes: These measures resulted in a rapid response and disease control. Lessons: Acute myeloid leukemia with the NUP98/RARG fusion gene and the RUNX1 mutation may be a special subtype of AML and may benefit from the alkaloid-based regimen.

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“…6 Since then, 9 additional cases of RARG rearrangement have been reported, including 2 with NUP98-RARG fusions. [7][8][9][10][11][12][13] Here we describe a case of NUP98-RARG gene fusion in an AML patient with the classic morphologic features and immunophenotype of APL.…”

Section: Introductionmentioning

confidence: 91%

<p>Acute Myeloid Leukemia with <em>NUP98-RARG</em> Gene Fusion Similar to Acute Promyelocytic Leukemia: Case Report and Literature Review</p>

Tao¹,

Song²,

Deng³

et al. 2020

OTT

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Retinoic acid receptor gamma (RARG) belongs to the nuclear receptor superfamily and has 90% homology to RAR alpha (RARA) and RAR beta. The promyelocytic leukemia (PML)-RARA fusion gene has been implicated in acute promyelocytic leukemia (APL). RARG gene rearrangement has been identified in a rare subtype of acute myeloid leukemia (AML) that resembles APL. To date, only 10 cases of gene rearrangements involving RARG (nucleoporin [NUP]98-RARG, promyelocytic leukemia protein-RARG, cleavage and polyadenylation-specific factor 6-RARG, or nucleophosmin [NPM]1-RARG-NPM1) have been reported. These patients show characteristics similar to APL, including bone marrow morphology, coagulation abnormality, and immunophenotype; however, they are resistant to all-trans retinoic acid and arsenic trioxide treatment. Moreover, there is no optimal therapeutic regimen for this subtype of AML. In this study, we report the clinical presentation and experimental findings of a case of AML with NUP98-RARG gene fusion similar to APL and review other cases of RARG gene rearrangement described in the literature.

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A novel entity of acute myeloid leukaemia with recurrent RARG-rearrangement resembling acute promyelocytic leukaemia

Cited by 18 publications

References 8 publications

Acute promyelocytic leukemia with a cryptic insertion of RARA into TBL1XR1

Acute promyelocytic leukemia with a cryptic insertion of RARA into TBL1XR1

Alkaloid-based regimen is beneficial for acute myeloid leukemia resembling acute promyelocytic leukemia with NUP98/RARG fusion and RUNX1 mutation

<p>Acute Myeloid Leukemia with <em>NUP98-RARG</em> Gene Fusion Similar to Acute Promyelocytic Leukemia: Case Report and Literature Review</p>

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