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Gene expression profiling of Down Syndrome (DS)-AMKL and non-DS AMKL samples

ABSTRACT: The goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia). A similar study was done previously, but using unfractionated patient leukemic samples. In this study, we sorted megakaryocytic leukemia blasts from patients and then compared their gene expression signatures to those from similarly sorted blasts from patients with non-DS AMKL. This allowed us to identify a gene expression signature more unique to DS-AMKL samples.

ORGANISM(S): Homo sapiens

PROVIDER: GSE16677 | GEO | 2010/08/01

SECONDARY ACCESSION(S): PRJNA122713

REPOSITORIES: GEO

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Gene expression profiling of Down Syndrome (DS)-AMKL and non-DS AMKL samples

Project description:The goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia). A similar study was done previously, but using unfractionated patient leukemic samples. In this study, we sorted megakaryocytic leukemia blasts from patients and then compared their gene expression signatures to those from similarly sorted blasts from patients with non-DS AMKL. This allowed us to identify a gene expression signature more unique to DS-AMKL samples. The leukemic blasts were sorted based on CD41, CD7, CD117, CD33, and CD34 antibodies as previously described (Klin. Padiatr. 217, 126-134).

2010-08-01 | E-GEOD-16677 | biostudies-arrayexpress

Expression data of human mesenchymal stromal cells isolated from bone marrow of ML-DS, AMKL patients and HD

Project description:Bone marrow fibrosis (BMF) is a rare complication in acute leukemia. In pediatrics, it predominantly occurs in acute megakaryoblastic leukemia (AMKL) and here especially in patients with trisomy 21, called myeloid leukemia in Down syndrome (ML-DS). Defects in mesenchymal stromal cells (MSCs) and cytokines specifically released by the myeloid blasts are the main drivers of fibrosis in the bone marrow niche (BMN). In order to determine which factors are necessary/sufficient for the BMF, we first established MSCs from pediatric patients with AMKL and ML-DS. Healthy donor (HD) control MSCs were established from children and adolescents ≤18 years of age. Steady-state analyses of the MSCs revealed that patient-derived MSCs exhibited decreased adipogenic differentiation potential, enrichment of proliferation-associated genes and upregulation of the oncofetal protein IF2B3. TGFB1 exposure in vitro promoted early profibrotic changes in all three MSC entities. To study BMF induction for longer periods of time, we created an in vivo humanized artificial BMN in immunodeficient mice. Injection of AMKL blasts as producers of TGFB1 specifically induced fibrosis grade I/II in a dose-dependent fashion, thus strongly suggesting TGFB1 excess to be sufficient for BMF. Our in vivo BMF model will be instrumental to specifically prevent the BMF and to identify potentially druggable target genes. We used microarrays to obtain a global overview of the differences between undifferentiated ML-DS- and AMKL-MSC compared to HD-MSC

2020-07-27 | GSE138861 | GEO

Global gene expression profile of primary human leukemic blasts

Project description:The goal of this study is to define the global gene expression profile of primary leukemic blasts from patients with different forms of myeloid leukemia and different FAB subtypes. Here we report the global gene expression profile of 2 patients with AML FAB M5, 2 patients with AML FAB M7, 3 patients with Down syndrome AML FAB M7 and 3 patients with Down syndrome transient leukemia.

2009-12-29 | GSE19681 | GEO

Developmental stage-specific interplay between GATA1 and IGF signaling in fetal hematopoiesis and leukemogenesis

Project description:This SuperSeries is composed of the following subset Series: GSE16676: Rescue of murine Gata1s mutant M7 leukemic cells by full-length Gata1 GSE16677: Gene expression profiling of Down Syndrome (DS)-AMKL and non-DS AMKL samples GSE16679: Plag1 overexpression cooperates with Evi1 overexpression and Gata1s mutation in leading to M7 leukemia GSE16682: Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors GSE16684: Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors depends on IGF signaling Refer to individual Series

2010-08-01 | E-GEOD-16655 | biostudies-arrayexpress

Murine M7 leukemia derived from retroviral insertional mutagenesis of Gata1s fetal progenitors

Project description:The goal of this study is to derive a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the hematopoietic transcription factor, GATA1 (called GATA1s mutation). We achieved this through transduction of Gata1s mutant fetal progenitors by MSCV-based retrovirus expressing a GFP marker, followed by in vitro selection (for immortalized cell lines), and then in vivo selection (for transformed cell lines) through transplantation. Here we report one such cell line [T6(6)] that gives rise to megakaryocytic leukemia (M7 leukemia) upon transplantation. Since the leukemic cells were retrovirally tagged with a GFP reporter, we sorted GFP+ leukemic blasts and generated their expression profiles by microarray.

2010-08-01 | E-GEOD-16682 | biostudies-arrayexpress

Role of trisomy 21, GATAs mutation and associated mutations in the development of a DS-AMKL model from IPSC: Cut&Tag

Project description:Acute megakaryoblastic leukemia of Down syndrome (DS-AMKL) is a model of clonal evolution from a preleukemic transient myeloproliferative disorder requiring both a trisomy 21 (T21) and a GATA1s mutation to a leukemia driven by additional driver mutations. We modelled this leukemic evolution through stepwise gene editing of GATA1s, SMC3+/- and MPLW515K providing 20 different trisomy or disomy 21 iPSC clones. Cut&Tag against GATA1 was performed on CD41+CD42+ megakaryocytes obtained after 18 days of differentiation of the IPSC clones. 500,000 CD41+CD42+ MK sorted cells were used to analyze GATA1 and GATA1s chromatin occupancy using the CUT&Tag-IT Assay Kit (Active Motif) according to the manufacturer recommendations. Briefly, cells were bound to Concanavalin A-Coated Beads and incubated with primary anti-GATA1 antibody in buffer with Protease Inhibitor Cocktail and 5% digitonine overnight at 4°C under rotation. The Guinea Pig anti-rabbit secondary antibody was incubated in Dig-Wash buffer for 1 hour at RT under rotation. After 3 washes, the CUT&Tag-IT™ Assembled pA-Tn5 Transposomes (1:100) were added for 1 hour at RT under rotation and tagmentation was performed during 1 hour at 37°C. DNA was purified and libraries were generated by PCR. The final libraries were purified, pooled together in equal concentrations and subjected to paired-end sequencing (100 cycles: 2x50) in Novaseq-6000 sequencer (Illumina) at Gustave Roussy.

2022-09-30 | E-MTAB-11032 | biostudies-arrayexpress

Role of trisomy 21, GATAs mutation and associated mutations in the development of a DS-AMKL model from IPSC: RNAseq

Project description:Acute megakaryoblastic leukemia of Down syndrome (DS-AMKL) is a model of clonal evolution from a preleukemic transient myeloproliferative disorder requiring both a trisomy 21 (T21) and a GATA1s mutation to a leukemia driven by additional driver mutations. We modeled this leukemic evolution through step-wise gene editing of GATA1s, SMC3+/- and MPLW515K providing 20 different trisomy or disomy 21 iPSC clones. For RNAseq, each condition was represented by a randomly selected clone and all the clones were isogenically compared. Cells were labeled with APC, BV421 and PE-conjugated antibodies against CD41a, CD42b and CD33 (see Table S5), respectively. In order to obtain a highly purified megakaryocytes, CD33+ cells were removed from the double positive CD41, CD42 population during cell sorting. After sorting, the purity was verified and corresponded to 98-100% of CD41+, CD42+, CD33. Total RNA was extracted using RNA/DNA/Protein Purification Plus Kit (Proteigene, St Marcel, France). Whole transcriptome sequencing was performed at the GenomEast Platform (Illkirch, France). cDNA libraries were synthesized from 250 ng total RNA using TruSeq Strandard mRNA Kit (Illumina). Libraries were verified for their amount and quality by capillary electrophoresis using a 2100 Bioanalyzer (Agilent Technologies). Sequencing was performed at 2100 bp using the Illumina HiSeq 4000 technology, yielding > 40 million reads per sample.

2022-09-29 | E-MTAB-11033 | biostudies-arrayexpress

Expression analysis of GATA1s murine megakaryocyte progenitors from bone marrow and fetal Liver

Project description:About 10% of Down syndrome (DS) infants are born with a myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). In order to understand differences that may exist between fetal and bone marrow megakaryocyte progenitor cell populations we flow sorted megakaryocyte progenitor cells and performed microarray expression analysis. kewywords: Mouse megakaryocyte progenitors

2013-03-29 | GSE45619 | GEO

Expression analysis of BL6 murine megakaryocyte progenitors from bone marrow and fetal Liver

2013-03-29 | GSE45618 | GEO

caArray_orkin-0038: Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling

Project description:Individuals with Down syndrome (DS) are predisposed to develop acute megakaryoblastic leukemia (AMKL), characterized by expression of truncated GATA1 transcription factor protein (GATA1s) due to somatic mutation. The treatment outcome for DS-AMKL is more favorable than for AMKL in non-DS patients. To gain insight into gene expression differences in AMKL, we compared 24 DS and 39 non-DS AMKL samples. We found that non-DS-AMKL samples cluster in two groups, characterized by differences in expression of HOX/TALE family members. Both of these groups are distinct from DS-AMKL, independent of chromosome 21 gene expression. To explore alterations of the GATA1 transcriptome, we used cross-species comparison with genes regulated by GATA1 expression in murine erythroid precursors. Genes repressed after GATA1 induction in the murine system, most notably GATA-2, MYC, and KIT, show increased expression in DS-AMKL, suggesting that GATA1s fail to repress this class of genes. Only a subset of genes that are up-regulated upon GATA1 induction in the murine system show increased expression in DS-AMKL, including GATA1 and BACH1, a probable negative regulator of megakaryocytic differentiation located on chromosome 21. Surprisingly, expression of the chromosome 21 gene RUNX1, a known regulator of megakaryopoiesis, was not elevated in DS-AMKL. Our results identify relevant signatures for distinct AMKL entities and provide insight into gene expression changes associated with these related leukemias.

2016-06-17 | GSE83449 | GEO

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