A novel mechanism of NPM1 cytoplasmic localization in acute myeloid leukemia: the recurrent gene fusion NPM1-HAUS1

Campregher, Paulo Vidal; Pereira, Welbert Oliveira; Lisboa, Bianca; Puga, Renato; Velloso, Elvira Deolinda Rodrigues Pereira; Helman, Ricardo; Marti, Luciana Cavalheiro; Guerra, João Carlos Campos; Manola, Kalliopi N.; Petroni, Roberta Cardoso; Bezerra, Alanna Mara Pinheiro Sobreira; Costa, Fernando Ferreira; Hamerschlak, Nelson; Santos, Fábio Pires de Souza

doi:10.3324/haematol.2015.137364

Cited by 15 publications

(7 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The NPM1-BRAF fusion encompasses almost all the coding sequence of NPM1, coding for nucleophosmin 1, a nucleolar phosphoprotein implicated in several pathways including mRNA transport, chromatin remodelling and genome stability. Recurrent NPM1-HAUS augmin-like complex, subunit 1 (HAUS1) fusions have been reported in acute myeloid leukaemia with a similar breakpoint in NPM1 exon 11 [48]. To prove the oncogenicity or specificity of this new NPM1-BRAF fusion is beyond the scope of this descriptive study.…”

Section: Discussionmentioning

confidence: 94%

Low‐grade epilepsy‐associated neuroepithelial tumours with a prominent oligodendroglioma‐like component: The diagnostic challenges

Métais

Appay

Pagès

et al. 2021

Neuropathology Appl Neurobio

View full text Add to dashboard Cite

Aims: We searched for recurrent pathological features and molecular alterations in a retrospective series of 72 low-grade epilepsy-associated neuroepithelial tumours (LEATs) with a prominent oligodendroglioma-like component, in order to classify them according to the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumours. Methods: Centralised pathological examination was performed as well as targeted molecular analysis of v-Raf murine sarcoma viral oncogene homologue B (BRAF) and fibroblast growth factor receptor 1 (FGFR1) by multiplexed digital polymerase chain reaction (mdPCR). DNA methylation profiling was performed in cases with sufficient DNA. In cases with no genetic alteration by mdPCR and sufficient material, RNA sequencing was done. Results: We first reclassified our cohort into three groups: ganglioglioma (GG, n = 14), dysembryoplastic neuroepithelial tumours (DNTs, n = 19) and glioneuronal tumours/ paediatric-type low-grade glioma (LGG) not otherwise specified (GNT/PLGG NOS, n = 39). mdPCR found an alteration in 38/72 cases. Subsequent RNA sequencing revealed a fusion transcript involving BRAF, FGFR1/2/3 or neurotrophic tyrosine kinase receptor type 2 [NTRK2] in 9/25 cases. DNA methylation profiling found 12/46 cases with a calibrated score ≥0.9. Unsupervised hierarchical clustering revealed two clusters: Cluster 1 was enriched with cases classified as DNT at histology, belonging to the LGG-DNT methylation class (MC), with haematopoietic progenitor cell antigen (CD34) negativity and FGRF1 alterations; Cluster 2 was enriched with cases classified at histology as GG, belonging to the LGG-GG MC MC, with BRAF V600E mutation and CD34 positivity. The tumours reclassified as GNT/PLGG NOS were equally distributed across both clusters. Interestingly, all polymorphous low-grade neuroepithelial tumour of the young Romain Appay and Mélanie Pagès contributed equally to this study.

show abstract

Section: Discussionmentioning

confidence: 94%

Low‐grade epilepsy‐associated neuroepithelial tumours with a prominent oligodendroglioma‐like component: The diagnostic challenges

Métais

Appay

Pagès

et al. 2021

Neuropathology Appl Neurobio

View full text Add to dashboard Cite

show abstract

“…NPM1 mutation is the most common gene mutation in AML, but it exhibits the mutual exclusion with PML-RARA , so it is absent in APL [ 116 ]. Besides of NPM1 mutation, NPM1 fusions, such as NPM1-MLF1 [ 117 ], NPM1-HAUS1 [ 118 ], NPM1-RARA [ 44 ], NPM1-RARG-NPM1 [ 112 ], were identified in AML. Among them, NPM1-RARA and NPM1-RARG-NPM1 were associated with variant APL, and they have been described in previous section of our review.…”

Section: Npm1 Rearrangement In Variant Aplmentioning

confidence: 99%

Current views on the genetic landscape and management of variant acute promyelocytic leukemia

Zhang

Sun

et al. 2021

Biomark Res

View full text Add to dashboard Cite

Acute promyelocytic leukemia (APL) is characterized by the accumulation of promyelocytes in bone marrow. More than 95% of patients with this disease belong to typical APL, which express PML-RARA and are sensitive to differentiation induction therapy containing all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), and they exhibit an excellent clinical outcome. Compared to typical APL, variant APL showed quite different aspects, and how to recognize, diagnose, and treat variant APL remained still challenged at present. Herein, we drew the genetic landscape of variant APL according to recent progresses, then discussed how they contributed to generate APL, and further shared our clinical experiences about variant APL treatment. In practice, when APL phenotype was exhibited but PML-RARA and t(15;17) were negative, variant APL needed to be considered, and fusion gene screen as well as RNA-sequencing should be displayed for making the diagnosis as soon as possible. Strikingly, we found that besides of RARA rearrangements, RARB or RARG rearrangements also generated the phenotype of APL. In addition, some MLL rearrangements, NPM1 rearrangements or others could also drove variant APL in absence of RARA/RARB/RARG rearrangements. These results indicated that one great heterogeneity existed in the genetics of variant APL. Among them, only NPM1-RARA, NUMA-RARA, FIP1L1-RARA, IRF2BP2-RARA, and TFG-RARA have been demonstrated to be sensitive to ATRA, so combined chemotherapy rather than differentiation induction therapy was the standard care for variant APL and these patients would benefit from the quick switch between them. If ATRA-sensitive RARA rearrangement was identified, ATRA could be added back for re-induction of differentiation. Through this review, we hoped to provide one integrated view on the genetic landscape of variant APL and helped to remove the barriers for managing this type of disease.

show abstract

“…This phenomenon was first described in chronic myeloid leukemia (CML) when researchers used quinacrine fluorescence and Giemsa staining, finding a cellular oncogene ABL1 on chromosome 9 fused to BCR on chromosome 22, forming BCR-ABL1 fusion gene on the newly formed Philadelphia chromosome. Later studies found that this gene fusion had changed this previously deadly type of cancer into the nearly cured disease using tyrosine kinase inhibitors [1] , [2] , [3] , [4] , [5] . Since then, with the development of biomedical technologies, more and more gene fusions were detected with further understanding of their mechanisms and biological functions.…”

Section: Introductionmentioning

confidence: 99%

Gene Fusion in Malignant Glioma: An Emerging Target for Next-Generation Personalized Treatment

Wang

Huang

et al. 2018

Translational Oncology

View full text Add to dashboard Cite

Malignant gliomas are heterogeneous diseases in genetic basis. The development of sequencing techniques has identified many gene rearrangements encoding novel oncogenic fusions in malignant glioma to date. Understanding the gene fusions and how they regulate cellular processes in different subtypes of glioma will shed light on genomic diagnostic approaches for personalized treatment. By now, studies of gene fusions in glioma remain limited, and no medication has been approved for treating the malignancy harboring gene fusions. This review will discuss the current characterization of gene fusions occurring in both adult and pediatric malignant gliomas, their roles in oncogenesis, and the potential clinical implication as therapeutic targets.

show abstract

A novel mechanism of NPM1 cytoplasmic localization in acute myeloid leukemia: the recurrent gene fusion NPM1-HAUS1

Cited by 15 publications

References 16 publications

Low‐grade epilepsy‐associated neuroepithelial tumours with a prominent oligodendroglioma‐like component: The diagnostic challenges

Low‐grade epilepsy‐associated neuroepithelial tumours with a prominent oligodendroglioma‐like component: The diagnostic challenges

Current views on the genetic landscape and management of variant acute promyelocytic leukemia

Gene Fusion in Malignant Glioma: An Emerging Target for Next-Generation Personalized Treatment

Contact Info

Product

Resources

About