A Case of a Novel PML/RARA Short Fusion Transcript with Truncated Transcription Variant 2 of the RARA Gene

Ježíšková, Ivana; Rázga, Filip; Gazdová, Jana; Doubek, Michael; Jurček, Tomáš; Korístek, Z; Mayer, Jiřı́; Dvořáková, Dana

doi:10.1007/bf03256361

Cited by 10 publications

(4 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Jeziskova et al also report a unique case with similar breakpoint but with a smaller intronic insertion (9 nucleotides). 20 Our patient showed a slightly delayed response to ATO based therapy, achieving complete molecular remission post consolidation as compared to the patient described by Jeziskova et al, who was in complete molecular remission post-ATRA based induction therapy.…”

Section: Discussionsupporting

confidence: 44%

Molecular Heterogeneity in Acute Promyelocytic Leukemia - A Single Centre Experience From India

Rabade

Raval

Subramanian

et al. 2018

Mediterr J Hematol Infect Dis

View full text Add to dashboard Cite

Atypical breakpoints and variant APL cases involving alternative chromosomal aberrations are seen in a small subset of acute promyelocytic leukemia (APL) patients. Over seven different partner genes for RARA have been described. Although rare, these variants prove to be a diagnostic challenge and require a combination of advanced cytogenetic and molecular techniques for accurate characterization. Heterogeneity occurs not only at the molecular level but also at clinico-pathological level influencing treatment response and outcome. In this case series, we describe the molecular heterogeneity of APL with a focus on seven variant APL cases from a single tertiary cancer center in India over a period of two and a half years.We discuss five cases with ZBTB16-RARA fusion and two novel PML-RARA variants, including a Bcr3 variant involving fusion of PML exon4 and RARA exon3 with an additional 40 nucleotides originating from RARA intron2, another involving exon 6 of PML and exon 3 of RARA with addition of 126 nucleotides, which mapped to the central portion of RARA intron 2. To the best of our knowledge, this is the first case series of this kind from India.

show abstract

Section: Discussionsupporting

confidence: 44%

Molecular Heterogeneity in Acute Promyelocytic Leukemia - A Single Centre Experience From India

Rabade

Raval

Subramanian

et al. 2018

Mediterr J Hematol Infect Dis

View full text Add to dashboard Cite

show abstract

“…Among others, a short insertion of nine nucleotides (CCCCCAGTT) of unknown origin has been reported in a PML-RARA fusion between PML exon 4 and part of the exon 1 of RARA2. This was the first time that a fusion transcript involving the alternative isoform of RARA was found in an APL patient [82].…”

Section: Pml-rara Atypical Isoformsmentioning

confidence: 85%

“…These rare bcr3 isoforms originate from breakpoints located downstream of PML exon 4, which is then commonly involved in the splicing with RARA exon 3 [73,74,[81][82][83]. In this case, as for bcr2 and bcr1 variants, insertions of genomic DNA sequences might also occur at the junction between PML and RARA genes [74,82,83]. Among others, a short insertion of nine nucleotides (CCCCCAGTT) of unknown origin has been reported in a PML-RARA fusion between PML exon 4 and part of the exon 1 of RARA2.…”

Section: Pml-rara Atypical Isoformsmentioning

confidence: 99%

Acute Promyelocytic Leukemia: A Constellation of Molecular Events around a Single PML-RARA Fusion Gene

Liquori

Ibáñez

Sargas

et al. 2020

Cancers

107

View full text Add to dashboard Cite

Although acute promyelocytic leukemia (APL) is one of the most characterized forms of acute myeloid leukemia (AML), the molecular mechanisms involved in the development and progression of this disease are still a matter of study. APL is defined by the PML-RARA rearrangement as a consequence of the translocation t(15;17)(q24;q21). However, this abnormality alone is not able to trigger the whole leukemic phenotype and secondary cooperating events might contribute to APL pathogenesis. Additional somatic mutations are known to occur recurrently in several genes, such as FLT3, WT1, NRAS and KRAS, whereas mutations in other common AML genes are rarely detected, resulting in a different molecular profile compared to other AML subtypes. How this mutational spectrum, including point mutations in the PML-RARA fusion gene, could contribute to the 10%-15% of relapsed or resistant APL patients is still unknown. Moreover, due to the uncertain impact of additional mutations on prognosis, the identification of the APL-specific genetic lesion is still the only method recommended in the routine evaluation/screening at diagnosis and for minimal residual disease (MRD) assessment. However, the gene expression profile of genes, such as ID1, BAALC, ERG, and KMT2E, once combined with the molecular events, might improve future prognostic models, allowing us to predict clinical outcomes and to categorize APL patients in different risk subsets, as recently reported. In this review, we will focus on the molecular characterization of APL patients at diagnosis, relapse and resistance, in both children and adults. We will also describe different standardized molecular approaches to study MRD, including those recently developed. Finally, we will discuss how novel molecular findings can improve the management of this disease.

show abstract

“…To our knowledge, 5 cases have been described, including the one with atypical fusion transcripts between PML exon 4 and RARA exon 3 (table 1) [4,7,8,9]. One reported case showed both an in-frame and an out-of-frame fusion of PML exon 4 and RARA exon 3 fusion transcript, while 3 other cases displayed only out-of-frame fusion transcripts.…”

Section: Figmentioning

confidence: 99%

Acute Promyelocytic Leukemia with a Rare PML Exon 4/RARA Exon 3 Fusion Transcript Variant

Park

Lee

et al. 2013

Acta Haematol

View full text Add to dashboard Cite

A Case of a Novel PML/RARA Short Fusion Transcript with Truncated Transcription Variant 2 of the RARA Gene

Cited by 10 publications

References 10 publications

Molecular Heterogeneity in Acute Promyelocytic Leukemia - A Single Centre Experience From India

Molecular Heterogeneity in Acute Promyelocytic Leukemia - A Single Centre Experience From India

Acute Promyelocytic Leukemia: A Constellation of Molecular Events around a Single PML-RARA Fusion Gene

Acute Promyelocytic Leukemia with a Rare <b><i>PML</i></b> Exon 4/<b><i>RARA</i></b> Exon 3 Fusion Transcript Variant

Contact Info

Product

Resources

About