scholarly journals Comprehensive molecular landscape in patients older than 80 years old diagnosed with acute myeloid leukemia: A study of the French Hauts-de-France AML observatory

2018 ◽  
Vol 94 (1) ◽  
pp. E24-E27 ◽  
Author(s):  
Loïc Renaud ◽  
Olivier Nibourel ◽  
Alice Marceau-Renaut ◽  
Bérengère Gruson ◽  
Nathalie Cambier ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Molecular Landscape ◽  
Acute Myeloid

scholarly journals Molecular Landscape of Acute Myeloid Leukemia: Prognostic and Therapeutic Implications

2020 ◽  
Vol 22 (6) ◽  
Author(s):  
Ludovica Marando ◽  
Brian J. P. Huntly
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Gene Mutations ◽  
Influence Strategies ◽  
Prognostic Information ◽  
Therapeutic Implications ◽  
Genomic Landscape ◽  
Genetic Landscape ◽  
Molecular Landscape ◽  
Acute Myeloid

Abstract Purpose of Review The field of acute myeloid leukemia (AML) has been revolutionized in recent years by the advent of high-throughput techniques, such as next-generation sequencing. In this review, we will discuss some of the recently identified mutations that have defined a new molecular landscape in this disease, as well as their prognostic, predictive, and therapeutic implications. Recent Findings Recent studies have shown how many cases of AML evolve from a premalignant period of latency characterized by the accumulation of several mutations and the emergence of one or multiple dominant clones. The pattern of co-occurring mutations and cytogenetic abnormalities at diagnosis defines risk and can determine therapeutic approaches to induce remission. Besides the genetic landscape at diagnosis, the continued presence of particular gene mutations during or after treatment carries prognostic information that should further influence strategies to maintain remission in the long term. Summary The recent progress made in AML research is a seminal example of how basic science can translate into improving clinical practice. Our ability to characterize the genomic landscape of individual patients has not only improved our ability to diagnose and prognosticate but is also bringing the promise of precision medicine to fruition in the field.

scholarly journals Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance

Blood ◽  
2016 ◽  
Vol 127 (1) ◽  
pp. 29-41 ◽  
Author(s):  
David Grimwade ◽  
Adam Ivey ◽  
Brian J. P. Huntly
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Treatment Options ◽  
Molecular Heterogeneity ◽  
Prognostic Information ◽  
Molecular Abnormalities ◽  
Disease Entities ◽  
Molecular Landscape ◽  
Individualization Of Therapy ◽  
Acute Myeloid

Abstract Recent major advances in understanding the molecular basis of acute myeloid leukemia (AML) provide a double-edged sword. Although defining the topology and key features of the molecular landscape are fundamental to development of novel treatment approaches and provide opportunities for greater individualization of therapy, confirmation of the genetic complexity presents a huge challenge to successful translation into routine clinical practice. It is now clear that many genes are recurrently mutated in AML; moreover, individual leukemias harbor multiple mutations and are potentially composed of subclones with differing mutational composition, rendering each patient’s AML genetically unique. In order to make sense of the overwhelming mutational data and capitalize on this clinically, it is important to identify (1) critical AML-defining molecular abnormalities that distinguish biological disease entities; (2) mutations, typically arising in subclones, that may influence prognosis but are unlikely to be ideal therapeutic targets; (3) mutations associated with preleukemic clones; and (4) mutations that have been robustly shown to confer independent prognostic information or are therapeutically relevant. The reward of identifying AML-defining molecular lesions present in all leukemic populations (including subclones) has been exemplified by acute promyelocytic leukemia, where successful targeting of the underlying PML-RARα oncoprotein has eliminated the need for chemotherapy for disease cure. Despite the molecular heterogeneity and recognizing that treatment options for other forms of AML are limited, this review will consider the scope for using novel molecular information to improve diagnosis, identify subsets of patients eligible for targeted therapies, refine outcome prediction, and track treatment response.

scholarly journals The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions

2017 ◽  
Vol 24 (1) ◽  
pp. 103-112 ◽  
Author(s):  
Hamid Bolouri ◽  
Jason E Farrar ◽  
Timothy Triche ◽  
Rhonda E Ries ◽  
Emilia L Lim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Pediatric Acute Myeloid Leukemia ◽  
Structural Alterations ◽  
Molecular Landscape ◽  
Acute Myeloid

Abstract C061: Molecular landscape of acute myeloid leukemia in Mexico

2020 ◽  
Author(s):  
Alexandra Gomez-Arteaga ◽  
Nuria Mencia-Trinchant ◽  
Adolfo Martinez Tovar ◽  
Irma Olarte Carrillo ◽  
Anel Garcia Laguna ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Molecular Landscape ◽  
Acute Myeloid

scholarly journals The molecular landscape of pediatric acute myeloid leukemia reveals recurrent structural alterations and age-specific mutational interactions

2017 ◽  
Author(s):  
Hamid Bolouri ◽  
Jason E. Farrar ◽  
Timothy Triche ◽  
Rhonda E. Ries ◽  
Emilia L. Lim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Immune Cell ◽  
Dna Hypermethylation ◽  
Pediatric Acute Myeloid Leukemia ◽  
Mirna Sequencing ◽  
Promoter Dna ◽  
Pediatric Aml ◽  
Molecular Landscape ◽  
Acute Myeloid

AbstractWe present the molecular landscape of pediatric acute myeloid leukemia (AML), characterizing nearly 1,000 participants in Children’s Oncology Group (COG) AML trials. The COG/NCI TARGET AML initiative assessed cases by whole-genome, targeted DNA, mRNA, miRNA sequencing and CpG methylation profiling. Validated DNA variants revealed diverse, infrequent mutations with fewer than 40 genes mutated in >2% of cases. In contrast, somatic structural variants, including novel gene fusions and focalMBNL1,ZEB2, andELF1deletions, were disproportionately prevalent in young as compared to adult patients. Conversely,DNMT3AandTP53mutations, common in adults, are conspicuously absent from virtually all pediatric cases. NovelGATA2,FLT3, andCBLmutations, recurrentMYC-ITD, NRAS, KRAS, andWT1mutations are frequent in pediatric AML. Deletions, mutations, and promoter DNA hypermethylation convergently impact Wnt signaling, Polycomb repression, innate immune cell interactions, and a cluster of zinc finger genes associated withKMT2Arearrangements. These results highlight the need for, and facilitate the development of age-tailored targeted therapies for the treatment of pediatric AML.

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