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A novel NUP98-JADE2 fusion in a patient with acute myeloid leukemia resembling acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia (AML) characterized by block of differentiation at the promyelocytic stage and the presence of PML-RARA fusion. In rare instances, RARA is fused with other partners in variant APL. More infrequently, non-RARA genes ar...

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Autores principales: Cheng, Chi-Keung, Chan, Hoi-Yun, Yung, Yuk-Lin, Wan, Thomas S. K., Leung, Alex W. K., Li, Chi-Kong, Tian, Ke, Chan, Natalie P. H., Cheung, Joyce S., Ng, Margaret H. L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Hematology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791568/
https://www.ncbi.nlm.nih.gov/pubmed/34673934
http://dx.doi.org/10.1182/bloodadvances.2021006064
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author Cheng, Chi-Keung
Chan, Hoi-Yun
Yung, Yuk-Lin
Wan, Thomas S. K.
Leung, Alex W. K.
Li, Chi-Kong
Tian, Ke
Chan, Natalie P. H.
Cheung, Joyce S.
Ng, Margaret H. L.
author_facet Cheng, Chi-Keung
Chan, Hoi-Yun
Yung, Yuk-Lin
Wan, Thomas S. K.
Leung, Alex W. K.
Li, Chi-Kong
Tian, Ke
Chan, Natalie P. H.
Cheung, Joyce S.
Ng, Margaret H. L.
author_sort Cheng, Chi-Keung
collection PubMed
description Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia (AML) characterized by block of differentiation at the promyelocytic stage and the presence of PML-RARA fusion. In rare instances, RARA is fused with other partners in variant APL. More infrequently, non-RARA genes are rearranged in AML patients resembling APL. However, the underlying disease pathogenesis in these atypical cases is largely unknown. Here, we report the identification and characterization of a NUP98- JADE2 fusion in a pediatric AML patient showing APL-like morphology and immunophenotype. Mechanistically, we showed that NUP98-JADE2 could impair all-trans retinoic acid (ATRA)-mediated transcriptional control and myeloid differentiation. Intriguingly, NUP98-JADE2 was found to alter the subcellular distribution of wild-type JADE2, whose down-regulation similarly led to attenuated ATRA-induced responses and myeloid activation, suggesting that NUP98-JADE2 may mediate JADE2 inhibition. To our knowledge, this is the first report of a NUP98-non-RAR rearrangement identified in an AML patient mimicking APL. Our findings suggest JADE2 as a novel myeloid player involved in retinoic acid-induced differentiation. Despite lacking a rearranged RARA, our findings implicate that altered retinoic acid signaling by JADE2 disruption may underlie the APL-like features in our case, corroborating the importance of this signaling in APL pathogenesis.
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spelling pubmed-87915682022-01-27 A novel NUP98-JADE2 fusion in a patient with acute myeloid leukemia resembling acute promyelocytic leukemia Cheng, Chi-Keung Chan, Hoi-Yun Yung, Yuk-Lin Wan, Thomas S. K. Leung, Alex W. K. Li, Chi-Kong Tian, Ke Chan, Natalie P. H. Cheung, Joyce S. Ng, Margaret H. L. Blood Adv Exceptional Case Report Acute promyelocytic leukemia (APL) is a specific subtype of acute myeloid leukemia (AML) characterized by block of differentiation at the promyelocytic stage and the presence of PML-RARA fusion. In rare instances, RARA is fused with other partners in variant APL. More infrequently, non-RARA genes are rearranged in AML patients resembling APL. However, the underlying disease pathogenesis in these atypical cases is largely unknown. Here, we report the identification and characterization of a NUP98- JADE2 fusion in a pediatric AML patient showing APL-like morphology and immunophenotype. Mechanistically, we showed that NUP98-JADE2 could impair all-trans retinoic acid (ATRA)-mediated transcriptional control and myeloid differentiation. Intriguingly, NUP98-JADE2 was found to alter the subcellular distribution of wild-type JADE2, whose down-regulation similarly led to attenuated ATRA-induced responses and myeloid activation, suggesting that NUP98-JADE2 may mediate JADE2 inhibition. To our knowledge, this is the first report of a NUP98-non-RAR rearrangement identified in an AML patient mimicking APL. Our findings suggest JADE2 as a novel myeloid player involved in retinoic acid-induced differentiation. Despite lacking a rearranged RARA, our findings implicate that altered retinoic acid signaling by JADE2 disruption may underlie the APL-like features in our case, corroborating the importance of this signaling in APL pathogenesis. American Society of Hematology 2022-01-17 /pmc/articles/PMC8791568/ /pubmed/34673934 http://dx.doi.org/10.1182/bloodadvances.2021006064 Text en © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
spellingShingle Exceptional Case Report
Cheng, Chi-Keung
Chan, Hoi-Yun
Yung, Yuk-Lin
Wan, Thomas S. K.
Leung, Alex W. K.
Li, Chi-Kong
Tian, Ke
Chan, Natalie P. H.
Cheung, Joyce S.
Ng, Margaret H. L.
A novel NUP98-JADE2 fusion in a patient with acute myeloid leukemia resembling acute promyelocytic leukemia
title A novel NUP98-JADE2 fusion in a patient with acute myeloid leukemia resembling acute promyelocytic leukemia
title_full A novel NUP98-JADE2 fusion in a patient with acute myeloid leukemia resembling acute promyelocytic leukemia
title_fullStr A novel NUP98-JADE2 fusion in a patient with acute myeloid leukemia resembling acute promyelocytic leukemia
title_full_unstemmed A novel NUP98-JADE2 fusion in a patient with acute myeloid leukemia resembling acute promyelocytic leukemia
title_short A novel NUP98-JADE2 fusion in a patient with acute myeloid leukemia resembling acute promyelocytic leukemia
title_sort novel nup98-jade2 fusion in a patient with acute myeloid leukemia resembling acute promyelocytic leukemia
topic Exceptional Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791568/
https://www.ncbi.nlm.nih.gov/pubmed/34673934
http://dx.doi.org/10.1182/bloodadvances.2021006064
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