Clinical and molecular features of acute promyelocytic leukemia with variant retinoid acid receptor fusions

Wen, Lijun; Xu, Yang; Li, Yao; Wang, Nana; Wang, Qinrong; Liu, Tianhui; Pan, Jinlan; Zhou, Hui; Miao, Miao; Shao, Yang; Wang, Xiaonan; Wang, Xiaoxia; Ruan, Changgeng; Wu, Depei; Chen, Suning

doi:10.3324/haematol.2018.205369

Cited by 33 publications

(38 citation statements)

References 15 publications

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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%

“…But we can confirm the resistance to ATO in this NUP98/RARG fusion gene-positive AML patient, similar to other reports. [ 3 4 ]…”

Section: Discussionmentioning

confidence: 99%

“…RUNX1 mutations occur in 13.7% of normal chromosome karyotype AML patients but rarely in APL patients. [ 1 3 ] In AML patients, the RUNX1 mutation is correlated with poor clinical outcomes, even when treatment with intensive therapeutic strategies is performed. [12] Our patient showed resistance to the standard 3 + 7 induction chemotherapy but benefitted from a homoharringtonine (HHT)-based combination.…”

Section: Discussionmentioning

confidence: 99%

“… [1] However, approximately 1.3% of acute myeloid leukemia (AML) patients present with features mimicking the classical hypergranular subtype of APL but without the typical PML/RAR α rearrangement. [ 2 3 ] Among them, a subtype of retinoic acid receptors ( RARs), RARG, has been reported to be fused with at least 3 alternative partner genes, including CPSF6, PML, and NUP98. [ 4 5 6 ] Herein, we report a nucleoporin 98-retinoic acid receptor gamma ( NUP98/RARG) gene fusion with a Runt (Runt domain)-related transcription factor 1 ( RUNX1 ) mutation in AML mimicking APL; it was sensitive to aalkaloid-based combination but insensitive to arsenic trioxide (ATO) or anthracycline.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…But we can confirm the resistance to ATO in this NUP98/RARG fusion gene-positive AML patient, similar to other reports. [ 3 4 ]…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Indeed, among the 19 resembling APL patients involved in their study, 15.79% (3/19) were insensitive and 63.16% (12/19) were resistant to ATRA treatment. Also, NGS performed on APL patients with alternative RARA or RARG fusions revealed more mutations of KMT2C , K-RAS , and GATA2 , but fewer mutations of FLT3-ITD when compared to APL patients with PML-RARA fusion [167].…”

Section: Alternative Rars-rearrangements Resemble Acute Promyelocimentioning

confidence: 99%

The Pleiotropic Role of Retinoic Acid/Retinoic Acid Receptors Signaling: From Vitamin A Metabolism to Gene Rearrangements in Acute Promyelocytic Leukemia

Conserva

Anelli

Zagaria

et al. 2019

IJMS

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The family of retinoic acid receptors (RARs: RARα, -β, and -γ) has remarkable pleiotropy characteristics, since the retinoic acid/RARs pathway is involved in numerous biological processes not only during embryonic development, but also in the postnatal phase and during adulthood. In this review, we trace the roles of RA/RARs signaling in the immune system (where this pathway has both an immunosuppressive role or is involved in the inflammatory response), in hematopoiesis (enhancing hematopoietic stem cell self-renewal, progenitor cells differentiation or maintaining the bone marrow microenvironment homeostasis), and in bone remodeling (where this pathway seems to have controversial effects on bone formation or osteoclast activation). Moreover, in this review is shown the involvement of RAR genes in multiple chromosomal rearrangements generating different fusion genes in hematological neoplasms, with a particular focus on acute promyelocytic leukemia and its variant subtypes. The effect of different RARs fusion proteins on leukemic transformation, on patients’ outcome, and on therapy response is also discussed.

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Identification of concurrent STAT3::RARA and RARA::STAT5b fusions in a variant APL case

Tao,

Cen,

et al. 2023

Molecular Carcinogenesis

Self Cite

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Acute promyelocytic leukemia (APL) with typically PML::RARA fusion gene caused by t (15;17) (q22; q12) was distinguished from other types of acute myeloid leukemia. In a subset of patients with APL, t (15;17) (q22;q21) and PML::RARA fusion cannot be detected. In this report, we identified the coexistence of STAT3::RARA and RARA::STAT5b fusions for the first time in a variant APL patient lacking t (15;17)(q22;q21)/PML::RARA fusion. Then, this patient was resistant to all‐trans retinoic acid combined arsenic trioxide chemotherapy. Accurate detection of RARA gene partners is crucial for variant APL, and effective therapeutic regime is urgently needed.

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Clinical and molecular features of acute promyelocytic leukemia with variant retinoid acid receptor fusions

Cited by 33 publications

References 15 publications

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

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

The Pleiotropic Role of Retinoic Acid/Retinoic Acid Receptors Signaling: From Vitamin A Metabolism to Gene Rearrangements in Acute Promyelocytic Leukemia

Identification of concurrent STAT3::RARA and RARA::STAT5b fusions in a variant APL case

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