This SuperSeries is composed of the SubSeries listed below.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part, Disease, Cell line, Treatment
View SamplesThe goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia).
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part, Disease, Cell line
View SamplesIn this project, we studied a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the GATA1 transcription factor (called GATA1s mutation). The model was generated through retroviral insertional mutagenesis in Gata1s mutant fetal liver progenitors. In this study, we analyzed the dependency of these leukemic cells on the Gata1s mutant protein.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part, Cell line, Treatment
View SamplesThe goal of this study is to develop a Plag1 signature and determine how its overexpression contributes to leukemogenesis.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Cell line
View SamplesThe 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.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part
View SamplesThe 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.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part
View SamplesThe 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.
miR-125b-2 is a potential oncomiR on human chromosome 21 in megakaryoblastic leukemia.
Specimen part, Disease
View SamplesThe goal of this study is to define miR-125b-2 target genes in the hematopoietic system by genetic alteration of miR-125b expression levels.
miR-125b-2 is a potential oncomiR on human chromosome 21 in megakaryoblastic leukemia.
Specimen part, Cell line
View SamplesErg is an ETS family transcription factor frequently overexpressed in human leukemias and has been implicated as a key regulator of hematopoietic stem cells (HSCs). However how Erg controls normal hematopoiesis, particularly at the stem cell level, remains poorly understood. Using homologous recombination, we generated an Erg knockdown allele (Ergkd) in which Erg expression can be restored upon Cre-mediated excision of a Stopper cassette. In Ergkd/+ mice, ~40% reduction in Erg dosage perturbed both fetal liver and bone marrow hematopoiesis by reducing the numbers of Lin-Sca-1+c-Kit+ (LSK) hematopoietic stem and progenitor cells (HSPCs) and megakaryocytic progenitors.
Reduced Erg Dosage Impairs Survival of Hematopoietic Stem and Progenitor Cells.
Specimen part
View SamplesWe report a mouse model that recapitulates expression of the ETV6-NTRK3 (EN) fusion oncoprotein, the product of the t(12;15)(p13;q25) translocation characteristic of human secretory breast carcinoma. Activation of EN expression in mammary tissues by Whey acidic protein (Wap) promoter-driven Cre leads to fully penetrant, multifocal malignant breast cancer with short latency. We provide genetic evidence that committed bipotent or CD61+ luminal alveolar progenitors, are targets of tumorigenesis. Furthermore, EN transforms these otherwise transient progenitors through activation of the AP1 complex. Given increasing relevance of chromosomal translocations in epithelial cancers, such mice serve as a paradigm for the study of their genetic pathogenesis and cellular origins, and generation of novel preclinical models.
ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex.
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