Acute myeloid leukemia in the elderly is characterized by a distinct genetic and epigenetic landscape

Silva, P; Neumann, Martin; Schroêder, M.; Vosberg, Sebastian; Schlee, Cornelia; Isaakidis, Konstandina; Ortiz-Tánchez, Jutta; Fransecky, Lars; Hartung, Teresa; Türkmen, Seval; Graf, Alexander; Krebs, Stefan; Blum, Helmut; Müller‐Tidow, Carsten; Thiede, Christian; Ehninger, Gerhard; Serve, Hubert; Hecht, Jochen; Berdel, Wolfgang E.; Greif, Philipp A.; Röllig, Christoph; Baldus, Claudia D.

doi:10.1038/leu.2017.109

Cited by 60 publications

(61 citation statements)

References 155 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We speculate that the reasons for the differences include the different number and age distribution of patients and possible ethnic differences among these cohorts (Supporting Information, Table S4). In accordance with previous studies, we also found that SF3B1 , ASXL1 , TET2 , and TP53 more frequently occurred in older patients rather than in younger patients. Recently, three genetic studies of large populations have revealed that somatic mutations in hematopoietic cells leading to clonal expansion are commonly acquired during human aging .…”

Section: Discussionsupporting

confidence: 93%

Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes

Liu

Jia

et al. 2017

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

U2AF1 mutations (U2AF1MT) occur commonly in myelodysplastic syndromes (MDS) without ring sideroblasts. The aim of this study was to investigate the clinical and biological implications of different U2AF1 mutation types in MDS. We performed targeted gene sequencing in a cohort of 511 MDS patients. Eighty-six patients (17%) were found to have U2AF1MT, which occurred more common in younger patients (P = .001) and represented ancestral lesions in a substantial proportion (71%) of cases. ASXL1MT and isolated +8 were significantly enriched in U2AF1MT-positive cases, whereas TP53MT, SF3B1MT, and complex karyotypes were inversely associated with U2AF1MT. U2AF subjects were enriched for isolated +8 and were inversely associated with complex karyotypes. U2AF1MT was significantly associated with anemia, thrombocytopenia, and poor survival in both lower-risk and higher-risk MDS. U2AF1 subjects had more frequently platelet levels of <50 × 10 /L (P = .043) and U2AF1 /U2AF1 subjects had more frequently hemoglobin concentrations at <80 g/L (P = .008) and more often overt fibrosis (P = .049). In conclusion, our study indicates that U2AF1MT is one of the earliest genetic events in MDS patients and that different types of U2AF1MT have distinct clinical and biological characteristics.

show abstract

Section: Discussionsupporting

confidence: 93%

Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes

Liu

Jia

et al. 2017

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

show abstract

“…22 In a recent study of elderly patients with acute myeloid leukemia, genes in the spliceosomal complex as well as TET2 were found to be altered more frequently than in younger cases, similar to what is seen in MDS. 23 While there are marked differences in the mutational spectrum between early onset MDS and MDS patients diagnosed at a traditional age, overall our results suggest that patients with MDS ≤50 years old constitute part of a continuum rather than a specific group with a distinct molecular pathogenesis. Increased frequency of TET2 mutations parallels the trend seen in healthy controls 17,20 with increasing frequency of TET2 mutations with aging suggesting a disease-initiating role of these mutations in MDS that is consistent with increased MDS risk in asymptomatic mutant carriers.…”

Section: Discussionmentioning

confidence: 54%

Molecular features of early onset adult myelodysplastic syndrome

et al. 2017

View full text Add to dashboard Cite

Myelodysplastic syndromes are typically diseases of older adults. Patients in whom the onset is early may have distinct molecular and clinical features or reflect a demographic continuum. The identification of differences between “early onset” patients and those diagnosed at a traditional age has the potential to advance understanding of the pathogenesis of myelodysplasia and may lead to formation of distinct morphological subcategories. We studied a cohort of 634 patients with various subcategories of myelodysplastic syndrome and secondary acute myeloid leukemia, stratifying them based on age at presentation and clinical parameters. We then characterized molecular abnormalities detected by next-generation deep sequencing of 60 genes that are commonly mutated in myeloid malignancies. The number of mutations increased linearly with age and on average, patients >50 years of age had more mutations. TET2, SRSF2, and DNMT3A were more commonly mutated in patients >50 years old compared to patients ≤50 years old. In general, patients >50 years of age also had more mutations in spliceosomal, epigenetic modifier, and RAS gene families. Although there are age-related differences in molecular features among patients with myelodysplasia, most notably in the incidence of SRSF2 mutations, our results suggest that patients ≤50 years old belong to a disease continuum with a distinct pattern of early onset ancestral events.

show abstract

“…Previous data indicate that the frequency of acquired somatic mutations increases with age (Silva et al , ; Li et al , ). To adjust for this, we compared clinical and laboratory variables and results of next generation sequencing (NGS) in these 59 patients with 236 age‐matched controls with MDS‐EB2 without Auer rods.…”

Section: Clinical and Laboratory Characteristics Of Mds‐eb2 Patients mentioning

confidence: 94%

Mutational features of myelodysplastic syndromes with Auer rods reveal them are more akin to acute myeloid leukemia

Huang

Qin

et al. 2019

Br J Haematol

View full text Add to dashboard Cite

Acute myeloid leukemia in the elderly is characterized by a distinct genetic and epigenetic landscape

Abstract: We stumble on a mystery and embrace it. We investigate and we doubt, but it would be ignorance to believe the inexplicable is impossible.In the end, our reward is a story worth telling. One that not only contributes to knowledge but also transforms us.

Cited by 60 publications

References 155 publications

Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes

Clinical features and biological implications of different U2AF1 mutation types in myelodysplastic syndromes

Molecular features of early onset adult myelodysplastic syndrome

Mutational features of myelodysplastic syndromes with Auer rods reveal them are more akin to acute myeloid leukemia

Contact Info

Product

Resources

About