Unknown,Transcriptomics,Genomics,Proteomics

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Rescue of murine Gata1s mutant M7 leukemic cells by full-length Gata1


ABSTRACT: In 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. Here we report Gata1s mutant leukemic cells were dependent on this mutant protein. Introduction of the full-length Gata1 protein to these cells led to their reduced proliferation and increased differentiation along the megakaryocytic lineage. We transduced leukemic cells with Gata1/estrogen receptor fusion cDNA (Gata1-ER) and generated stable cell lines. Addition of beta-estradiol to culture medium led to activation of the full-length Gata1 protein in synchronized leukemic cells. Gene expression profiles were collected at multiple time points.

ORGANISM(S): Mus musculus

SUBMITTER: Zhe Li 

PROVIDER: E-GEOD-16676 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.

Klusmann Jan-Henning JH   Godinho Frank J FJ   Heitmann Kirsten K   Maroz Aliaksandra A   Koch Mia Lee ML   Reinhardt Dirk D   Orkin Stuart H SH   Li Zhe Z  

Genes & development 20100801 15


Oncogene-mediated transformation of hematopoietic cells has been studied extensively, but little is known about the molecular basis for restriction of oncogenes to certain target cells and differential cellular context-specific requirements for oncogenic transformation between infant and adult leukemias. Understanding cell type-specific interplay of signaling pathways and oncogenes is essential for developing targeted cancer therapies. Here, we address the vexing issue of how developmental restr  ...[more]

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