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Multiplex Enhanced Reduced Representation Bisulfite Sequencing (mERRBS) longitudinal analysis of adult Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) with 1q jumping translocation after 5'-azacytidine treatment compared to controls

ABSTRACT: Jumping translocations are cytogenetic abnormalities associated with poor clinical outcome and progression in Myelodysplastic Syndromes/Acute Myeloid Leukemia (MDS/AML).Typically a donor chromosome, often a trisomic 1q, is transferred onto 2 or more recipient chromosomes. Previous studies have demonstrated the crosstalk between DNA hypomethylation and 1q trisomy. Here, we used an epi-genomic approach in sequential samples from a cohort of MDS and AML with the appearance of 1q jumping translocations after 5’-azacytidine (AZA) treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE271912 | GEO | 2025/07/01

REPOSITORIES: GEO

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Project description:Full Title: Multilineage Dysplasia (MLD) in AML correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: A comparison of 408 cases classified as “AML not otherwise specified” or “AML with myelodysplasia-related changes” The WHO classification of acute myeloid leukemia (AML) is hierarchically structured and integrates genetic information, data on patients’ history, and multilineage dysplasia (MLD). The category “AML with MDS-related changes” (AML-MRC) is separated from AML not otherwise specified (AML-NOS) by the presence of either MLD, MDS-related cytogenetics or MDS history. To clarify whether MLD alone is clinically relevant, we analyzed 408 adult patients categorized as AML-MRC or AML-NOS. EFS (Median 13.8 months vs. 16.0 months) and 3-year-OS (45.8% vs. 53.9%) did not differ significantly between patients with MLD and without. However, MLD correlated with pre-existing MDS (p<0.001) and MDS-related cytogenetics (p=0.035). Patients with MLD as sole AML-MRC criterion (AML-MLD-sole; n=90) had less frequently FLT3-ITD (p=0.032), and a lower median age than AML-NOS (n=232), but EFS, OS, and WBC did not differ significantly. Contrarily, patients with AML-NOS plus AML-MLD-sole (n=323) versus patients with MDS history or MDS-related cytogenetics (n=85) had better EFS (16.9 vs. 10.7 months; p=0.005) and 3-year-OS (55.8% vs. 32.5%; p=0.001). Gene expression profiles were measured for a subset of 96 patients. Analysis of the expression data showed distinct clusters for AML-MLD-sole and AML-NOS versus AML with MDS-related cytogenetics or MDS history. Thus, MLD demonstrated no independent clinical impact, while cytogenetics and MDS history were of prognostic relevance. This data suggest modifications in a revised WHO proposal. All 96 bone marrow samples were obtained from untreated patients at the time of diagnosis. Cells used for microarray analysis were collected from the purified fraction of mononuclear cells after Ficoll density centrifugation.

Dataset Information

Multiplex Enhanced Reduced Representation Bisulfite Sequencing (mERRBS) longitudinal analysis of adult Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) with 1q jumping translocation after 5'-azacytidine treatment compared to controls

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