Myelodysplastic syndromes (MDS) are associated with a high risk of transformation to acute myeloid leukemia (AML), with a 5-year transformation risk of roughly 20%. It is not yet well understood what the events are which cause transformation on MDS stem cells (MDS-SCs) into leukemic stem cells (LSCs). Studies leveraging whole genome sequencing have demonstrated that transformation from MDS to AML is defined by the persistence of a founder clones containing a large number of somatic mutations, and the emergence or growth of at least one subclone with novel mutations. Further studies have found that secondary AMLs are enriched with mutations in FLT3, NPM1, NRAS, PTPN11 ,WT1 IDH1 and IDH2, and that MDS patients with mutations in one of these genes have a faster transformation to AML.
Given the decreased survival rate which is associated with MDS transformation to AML, it is crucial to understand the mechanisms underlying transformation, with the goal of ultimately preventing transformation altogether. Many models have been suggested, including a linear model in which MDS-SCs evolve into SLCs, and a parallel model which hypothesized that quiescence of malignant stem cells enabled the accumulation of genetic abnormalities while aging. Furthermore, a study employing single-cell sequencing techniques reported that clonal evolution in the stem cell compartment appeared to be non-linear during MDS initiation and transformation
The aim of this collection is to gather papers exploring the pathophysiology of MDS transformation to AML which contribute to furthering our understanding of this mechanism. The collection will welcome Original Research, Review and Mini-Review articles.
Important Note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.
Myelodysplastic syndromes (MDS) are associated with a high risk of transformation to acute myeloid leukemia (AML), with a 5-year transformation risk of roughly 20%. It is not yet well understood what the events are which cause transformation on MDS stem cells (MDS-SCs) into leukemic stem cells (LSCs). Studies leveraging whole genome sequencing have demonstrated that transformation from MDS to AML is defined by the persistence of a founder clones containing a large number of somatic mutations, and the emergence or growth of at least one subclone with novel mutations. Further studies have found that secondary AMLs are enriched with mutations in FLT3, NPM1, NRAS, PTPN11 ,WT1 IDH1 and IDH2, and that MDS patients with mutations in one of these genes have a faster transformation to AML.
Given the decreased survival rate which is associated with MDS transformation to AML, it is crucial to understand the mechanisms underlying transformation, with the goal of ultimately preventing transformation altogether. Many models have been suggested, including a linear model in which MDS-SCs evolve into SLCs, and a parallel model which hypothesized that quiescence of malignant stem cells enabled the accumulation of genetic abnormalities while aging. Furthermore, a study employing single-cell sequencing techniques reported that clonal evolution in the stem cell compartment appeared to be non-linear during MDS initiation and transformation
The aim of this collection is to gather papers exploring the pathophysiology of MDS transformation to AML which contribute to furthering our understanding of this mechanism. The collection will welcome Original Research, Review and Mini-Review articles.
Important Note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) will not be accepted in any of the sections of Frontiers in Oncology.