Treatment of myelodysplastic syndrome in the era of next‐generation sequencing

Tobiasson, Magnus; Kittang, Astrid Olsnes

doi:10.1111/joim.12893

Cited by 17 publications

(19 citation statements)

References 222 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Considering the high incidence of mutations and cytogenetic alterations, it can be assumed that genomic instability plays a role in MDS pathogenesis [45]. Genomic instability is defined as the increased susceptibility of cells to acquire and spread genomic mutations or the inability of cells to deal with DNA damage [46].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Gene mutational analysis by NGS and its clinical significance in patients with myelodysplastic syndrome and acute myeloid leukemia

et al. 2020

Exp Hematol Oncol

View full text Add to dashboard Cite

Background: In this study, we retrospectively summarized the differences of molecular gene mutations between MDS and AML patients, as well as the young and older age groups of MDS and AML patients. We also analyzed the response of newly diagnosed AML patients to standard DA or IA induction chemotherapy and the relationship between the chemotherapy outcome and the frequency of different gene mutation abnormalities. Methods: NGS assay covering 43 genes was studied in 93 de novo MDS and 325 non-M3 AML patients. Bone marrow samples from all patients underwent gene mutational analysis by NGS. Results: At least one non-synonymous gene mutation was detected in 279 AML patients (85.8%) and 85 MDS patients (91.4%). Contrary to 59 years and younger AML patients, there was a significantly higher incidence of gene mutation in 60 years and older AML patients (2.37 vs 1.94, p = 0.034). Gene mutation incidence in 60 years and older MDS patients increased, but no statistical significance was present (1.95 vs 1.64, p = 0.216). AML patients had a significantly higher gene mutation incidence compared with MDS-MLD patients (2.02 vs 1.63, p = 0.046). Gene mutation incidence was higher in patients with MDS-EB1/EB2 compared with patients with MDS-MLD but there was no statistical significance present (2.14 vs 1.63, p = 0.081). AML patients had significantly higher incidences of CEBPA, FLT3-ITD, DNMT3A, NPM1 and IDH1/2 gene mutations (p = 0.0043, 0.000, 0.030962, 0.002752, and 0.000628, respectively) and a lower incidence of TET2 and U2AF1 gene mutations (p = 0.000004 and 0.000, respectively) compared with MDS patients. Among the individual genes in different age groups, there were significantly higher incidences of RUNX1, IDH2, TP53 and SF3B1 gene mutations (p = 0.0478, 0.0028, 0.0024 and 0.005, respectively) as well as a trend of higher ASXL gene mutation (p = 0.057) in 60 years and older AML patients compared to 59 years and younger patients. There was no statistically significant difference in MDS patients with the different age groups and among the individual genes. Between AML patients and MDS patients among the different gene functional groups, AML patients had a significantly higher incidence of transcriptional deregulation (27.4% vs 15.1%, p = 0.014963), activated signalling (36.3% vs 10.8%, p = 0.000002) related gene mutations as well as a significantly lower incidence of RNA spliceosome (6.15% vs 60.1%, p = 0.000) related gene mutations. Furthermore, among the patients who received either IA or DA regimen

show abstract

Section: Discussionmentioning

confidence: 99%

“…This interpretation must be taken into consideration for aspects such as cytogenetic data and basic disease characteristics as well as other molecular issues (e.g. epigenetics and gene expression) [45].…”

Section: Discussionmentioning

confidence: 99%

Gene mutational analysis by NGS and its clinical significance in patients with myelodysplastic syndrome and acute myeloid leukemia

et al. 2020

Exp Hematol Oncol

View full text Add to dashboard Cite

show abstract

“…At present, NGS is rarely incorporated into clinical guidelines although an increasing number of studies have demonstrated the benefit of using NGS in the clinical management of MDS patients [32].…”

Section: Myelodysplasic Syndromementioning

confidence: 99%

Haematological Malignancies: Overview of the Recent Progresses in Genetics

Bendari¹,

Sraidi²,

Khoubila³

2021

Cytogenetics - Classical and Molecular Strategies for Analysing Heredity Material

View full text Add to dashboard Cite

Genetic defects play a major role in pathogenesis of the most of haematological malignancies, including cytogenetic abnormalities, gene mutations, and abnormal gene expression. Our knowledge about the genetics of haematological disorders has been dramatically improved during the past decade, due to revolution of sequencing technologies which have played a crucial role. In this chapter, we describe the techniques commonly employed for elucidating chromosomal aberrations, prognostic impact of recurrent chromosomal abnormalities, and recently updated risk stratification systems. We will summarise the chromosomal abnormalities recently identified on many of haematological diseases such acute myeloid leukaemia, acute lymphoid leukaemia, myelodysplasic syndrome, multiple myeloma, meyloproliferative disease and clarify their impacts on clinical phenotype and prognosis, as well as their role in the pathogenesis of these diseases. The aim of this chapter is to provide a brief overview of the recent progresses in haematological diseases genetics.

show abstract

“…Identification of mutations associated with a poor prognosis when treated with conventional agents including chemotherapy has led to investigations of novel targeted agents. Examples include the use of the BCL2 inhibitor venetoclax in TP53-mutated disease and IDH1/2 inhibitors in IDH-mutated MDS [60].…”

Section: Myelodysplastic Syndromesmentioning

confidence: 99%

Application of Genomics to Clinical Practice in Haematological Malignancy

et al. 2019

View full text Add to dashboard Cite

Purpose of Review The usual abundance of fresh cells and high-quality DNA derived from bone marrow aspirate and peripheral blood mean haematological malignancies are at the forefront of the application of genomics to malignancy. This review evaluates where genomics is routinely used in clinical care and where opportunities for further application exist. Recent Findings The 2016 revision of the WHO classification of tumours of haematopoietic and lymphoid tissues increased the number of disease entities defined by, or whose diagnosis was strongly supported by, a specific genetic change. Increasingly combinations of mutations rather than individual lesions are being used to genomically classify heterogeneous disorders to inform prognosis and direct treatment. Furthermore, the role of different genetic aberrations as markers of measurable residual disease is being evaluated in clinical trials to allow intensification/de-intensification of treatment as appropriate and early detection of relapse. Summary Implementation of broader sequencing technologies such as whole exome/genome sequencing coupled with continuing developments in genomic technology to improve turnaround times are likely to further reinforce the centrality of genomics in the management of haematological malignancies.

show abstract

Treatment of myelodysplastic syndrome in the era of next‐generation sequencing

Abstract: Tobiasson M, Kittang AO (Karolinska

Cited by 17 publications

References 222 publications

Gene mutational analysis by NGS and its clinical significance in patients with myelodysplastic syndrome and acute myeloid leukemia

Gene mutational analysis by NGS and its clinical significance in patients with myelodysplastic syndrome and acute myeloid leukemia

Haematological Malignancies: Overview of the Recent Progresses in Genetics

Application of Genomics to Clinical Practice in Haematological Malignancy

Contact Info

Product

Resources

About