Karyotype evolution and acquisition of FLT3 or RAS pathway alterations drive progression of myelodysplastic syndrome to acute myeloid leukemia

Meggendorfer, Manja; Albuquerque, Andreia; Nadarajah, Nirsoshan; Alpermann, Tamara; Kern, Wolfgang; Steuer, Kimberly; Perglerová, Karolína; Haferlach, Claudia; Schnittger, Susanne; Haferlach, Torsten

doi:10.3324/haematol.2015.127985

Cited by 27 publications

(27 citation statements)

References 14 publications

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“…In addition to functional significance, recent sequencing technology also uncovered clonal dynamics based on detailed information of mutated clone size. In particular, multiple samples tested at serial time points in each case can conclude acquisition timing of each mutation, clonal architecture, and intratumor heterogeneity in myelodysplasia [4,[17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Somatic SETBP1 mutations in myeloid neoplasms

Makishima

2017

Int J Hematol

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Section: Introductionmentioning

confidence: 99%

Somatic SETBP1 mutations in myeloid neoplasms

Makishima

2017

Int J Hematol

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“…During this shift in clonal composition, no therapy other than erythropoiesis-stimulating agent was given. Previous reports have implicated RAS mutations in enhancement of proliferation and progression towards sAML 17 18 19 20 . Together with our data, this may indicate that screening for mutations in RAS family members is warranted in MDS, as acquisition of these mutations seems to correlate with the development of more aggressive clones that eventually may result in progression towards sAML.…”

Section: Discussionmentioning

confidence: 94%

Clonal evolution in myelodysplastic syndromes

et al. 2017

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Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5–11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment. The application of disease-modifying therapy may create an evolutionary bottleneck after which more complex MDS, but also unrelated clones of haematopoietic cells, may emerge. In addition, subclones that acquired an additional mutation associated with treatment resistance (TP53) or disease progression (NRAS, KRAS) may be detected months before clinical changes become apparent. Monitoring the genetic landscape during the disease may help to guide treatment decisions.

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“…Interestingly, 26 cases acquired mutations and of these, 18 remained cytogenetically normal, including all 12 patients with acquired KRAS or NRAS mutations. In comparing these MDS patients who transformed to AML, with their control cohort of MDS patients from a previous study who did not progress to AML 54 , the investigators found that mutations in ASXL1, ETV6, GATA2, IDH2, NRAS, RUNX1, and SRSF2 genes were more frequent in the MDS cases that progressed to AML, than in the control MDS cohort, suggesting that mutations in these genes predispose to transformation to secondary AML 55 .…”

Section: Secondary Amlmentioning

confidence: 99%

“…Mutations in 8 genes, including 4 spliceosome genes, SRSF2, SF3B1, U2AF1, and ZRSR2, 3 chromatin modifier genes, ASXL1, EZH2, and BCOR, and one cohesion complex gene, STAG2, showed >95% specificity for secondary AML as compared to de novo AML 46 . Since these 8 genes are also commonly mutated in MDS [47][48][49][50][51][52][53][54] , it was suggested that these mutations may primarily drive the myelodysplastic disease and not overt AML. Correlation with clinicopathologic features of the antecedent MDS (extent of bone marrow dysplasia or lineages involved by cytopenias) was not given in this study 46 .…”

Section: Secondary Amlmentioning

confidence: 99%

Acute myeloid leukemia in the era of precision medicine: recent advances in diagnostic classification and risk stratification

Kansal¹

2016

Cancer Biology &Amp; Medicine

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Acute myeloid leukemia (AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification of AML requires clinical and pathologic information, the latter including morphologic, immunophenotypic, cytogenetic and molecular genetic analysis. Risk stratification in AML requires cytogenetics evaluation as the most important predictor, with genetic mutations providing additional necessary information. AML with normal cytogenetics comprises about 40%-50% of all AML, and has been intensively investigated. The currently used 2008 World Health Organization classification of hematopoietic neoplasms has been proposed to be updated in 2016, also to include an update on the classification of AML, due to the continuously increasing application of genomic techniques that have led to major advances in our knowledge of the pathogenesis of AML. The purpose of this review is to describe some of these recent major advances in the diagnostic classification and risk stratification of AML.

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Karyotype evolution and acquisition of FLT3 or RAS pathway alterations drive progression of myelodysplastic syndrome to acute myeloid leukemia

Cited by 27 publications

References 14 publications

Somatic SETBP1 mutations in myeloid neoplasms

Somatic SETBP1 mutations in myeloid neoplasms

Clonal evolution in myelodysplastic syndromes

Acute myeloid leukemia in the era of precision medicine: recent advances in diagnostic classification and risk stratification

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