Somatic mutation involving activated signaling, transcription, or tumor suppression is a premise of MDS evolving into AML
Li, X.; Chang, C.-K.; Xu, F.; Wu, L.-Y.; Guo, J.; He, Q.; Zhang, Z.
Show abstract
The transformation biology of secondary AML from MDS is still not fully understood. Here, we performed a large cohort of paired sequences including target, whole-exome and single cell sequencing to search AML transformation-related mutations (TRM). The results showed that fifty-five out of the 64 (85.9%) patients presented presumptive TRM involving activated signaling, transcription factors, or tumor suppressors. Most of TRM (63.6%, 35 cases) emerged at the leukemia transformation point. All five of the remaining nine patients analyzed by paired whole exome sequencing showed TRM which are not included in the reference targets. Single-cell sequencing indicated that the activated cell signaling route was related to TRM which take place prior to phenotypic development. Of note, defined TRM was limited to a small set of genes (less than ten, in the order: NRAS/KRAS, CEBPA, TP53, FLT3, RUNX1, CBL, PTPN11 and WT1, accounted for 91.0% of the mutations). In conclusion, somatic mutations involving in activated signaling, transcription factors, or tumor suppressors appeared to be a precondition for AML transformation from myelodysplastic syndromes. The TRM may be considered as new therapy targets.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Mutational Profile Enables The Identification Of A High Risk Subgroup In Myelodysplastic Syndromes With Isolated Trisomy 8 96%
- ARPP19 promotes MYC expression and associates with patient relapse in acute myeloid leukemia 96%
- Tyrosine kinase inhibitor independent gene expression signature in CML offers new targets for LSPC eradication therapy 95%
Similar papers in this journal
- Analytical validation and performance characteristics of a 48-gene next-generation sequencing panel for detecting potentially actionable genomic alterations in myeloid neoplasms 95%
- Prediction of myeloid malignant cells in Fanconi anemia using machine learning 95%
- Bone marrow stromal cells induce an ALDH+ stem cell-like phenotype in AML cells through TGF-β-p38-ALDH2 pathway 94%
Similar papers in this journal
- Cas9-directed long-read sequencing to resolve optical genome mapping findings in leukemia diagnostics. 94%
- Stratified computational meta-analysis of 2213 acute myeloid leukemia patients reveals age- and sex-dependent gene expression signatures 94%
- STAT5-dependent regulation of CDC25A by miR-16 controls proliferation and differentiation in FLT3-ITD acute myeloid leukemia 94%
Similar papers in this journal
- RAG1 and RAG2 Non-core Regions Are Implicated in Leukemogenesis and Off-target V(D)J Recombination in BCR-ABL1-driven B-cell Lineage Lym-phoblastic Leukemia 94%
- A single microRNA miR-195 rescues the arrested B cell development induced by EBF1 deficiency 92%
- IDH1 regulates human erythropoiesis by eliciting chromatin state reprogramming 91%
Similar papers in this journal
- DOT1L methyltransferase regulates the calcium influx in erythroid progenitor cells in response to erythropoietin 92%
- Identification of ATP2B4 regulatory element containing functional genetic variants associated with severe malaria 91%
- Metabolite patterns in human myeloid hematopoiesis result from lineage-dependent active metabolic pathways 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.