Related Experiment Video
Updated: Apr 19, 2026
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
Integrated differential transcriptome maps of Acute Megakaryoblastic Leukemia (AMKL) in children with or without Down
Maria Chiara Pelleri1, Allison Piovesan2, Maria Caracausi3
1Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Unit of Histology, Embryology and Applied Biology, University of Bologna, Via Belmeloro 8, 40126, Bologna, BO, Italy. mariachiara.pelleri2@unibo.it.
Insights
This study reveals key gene expression changes in pediatric Acute Megakaryoblastic Leukemia (AMKL), particularly in children with Down Syndrome (DS). It identifies potential new clinical markers for AMKL progression and highlights the role of chromosome 21 genes.
Area of Science:
- Hematology
- Genomics
- Pediatric Oncology
Background:
- Acute Megakaryoblastic Leukemia (AMKL) is significantly more common in children with Down Syndrome (DS).
- The specific role of trisomy 21 in the development of AMKL in DS patients remains unclear.
- Previous gene expression studies in AMKL were limited by small sample sizes.
Purpose of the Study:
- To create integrated transcriptome maps of pediatric AMKL using meta-analysis.
- To investigate gene expression changes during the transition from normal megakaryocytes (MK) to pre-leukemic (TMD) and leukemic (AMKL) states in DS and non-DS children.
- To identify potential clinical markers for AMKL progression.
Main Methods:
- Systematic meta-analysis of publicly available gene expression datasets for pediatric AMKL.
- Utilized TRAM (Transcriptome Mapper) for integrating diverse data sources and platforms.
- Analyzed gene expression profiles from normal megakaryocytes (MK), Transient Myeloproliferative Disorder (TMD), DS AMKL, and non-DS AMKL samples.
Main Results:
- Developed a biological model of transcriptome changes from MK to TMD and DS AMKL.
- Identified repressed genes involved in megakaryocyte differentiation, including PF4, PPBP, MAP3K10, and MPL.
- Discovered TMEM241 as the most over-expressed gene and APOC2 and ZNF587B as discriminant markers for DS AMKL progression.
- Observed significant over-expression of chromosome 21 genes in TMD and both DS and non-DS AMKL, suggesting their critical role.
Conclusions:
- Presented an integrated transcriptome model for DS AMKL.
- Identified novel genes implicated in AMKL pathophysiology.
- Highlighted potential new clinical markers for AMKL, particularly in DS patients.
Background:
The incidence of Acute Megakaryoblastic Leukemia (AMKL) is 500-fold higher in children with Down Syndrome (DS) compared with non-DS children, but the relevance of trisomy 21 as a specific background of AMKL in DS is still an open issue. Several Authors have determined gene expression profiles by microarray analysis in DS and/or non-DS AMKL. Due to the rarity of AMKL, these studies were typically limited to a small group of samples.
Methods:
We generated integrated quantitative transcriptome maps by systematic meta-analysis from any available gene expression profile dataset related to AMKL in pediatric age. This task has been accomplished using a tool recently described by us for the generation and the analysis of quantitative transcriptome maps, TRAM (Transcriptome Mapper), which allows effective integration of data obtained from different experimenters, experimental platforms and data sources. This allowed us to explore gene expression changes involved in transition from normal megakaryocytes (MK, n=19) to DS (n=43) or non-DS (n=45) AMKL blasts, including the analysis of Transient Myeloproliferative Disorder (TMD, n=20), a pre-leukemia condition.
Results:
We propose a biological model of the transcriptome depicting progressive changes from MK to TMD and then to DS AMKL. The data indicate the repression of genes involved in MK differentiation, in particular the cluster on chromosome 4 including PF4 (platelet factor 4) and PPBP (pro-platelet basic protein); the gene for the mitogen-activated protein kinase MAP3K10 and the thrombopoietin receptor gene MPL. Moreover, comparing both DS and non-DS AMKL with MK, we identified three potential clinical markers of progression to AMKL: TMEM241 (transmembrane protein 241) was the most over-expressed single gene, while APOC2 (apolipoprotein C-II) and ZNF587B (zinc finger protein 587B) appear to be the most discriminant markers of progression, specifically to DS AMKL. Finally, the chromosome 21 (chr21) genes resulted to be the most over-expressed in DS and non-DS AMKL, as well as in TMD, pointing out a key role of chr21 genes in differentiating AMKL from MK.
Conclusions:
Our study presents an integrated original model of the DS AMLK transcriptome, providing the identification of genes relevant for its pathophysiology which can potentially be new clinical markers.
More Related Videos
09:01Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up
Published on: March 26, 2018
09:57Comprehensive Protocol to Sample and Process Bone Marrow for Measuring Measurable Residual Disease and Leukemic Stem Cells in Acute Myeloid Leukemia
Published on: March 5, 2018