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

Rabade, Nikhil; Raval, Goutham; Subramanian, Papagudi Ganesan; Kodgule, Rohan; Joshi, Shalik Ram; Tembhare, Prashant; Hasan, Syed Khizer; Jain, Hasmukh; Sengar, Manju; Narula, Gaurav; Banavali, Shripad; Kadam, Pratibha Amare; Shetty, Dhanalaxmi; Gujral, Sumeet; Patkar, Nikhil

doi:10.4084/mjhid.2018.002

Cited by 8 publications

(2 citation statements)

References 24 publications

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“…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

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et al. 2020

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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.

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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

show abstract

“…If diagnosed quickly, APL has a favorable prognosis with good responses to treatment. (5)(6)(7) Leukemias have complex genetic characteristics, hindering the initial analysis of different genes involved in the disease. This makes diagnosis difficult, negatively interfering in the initial stages of therapeutic approaches.…”

Section: ❚ Introductionmentioning

confidence: 99%