Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1207470 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Oncogenic NRAS mutations are frequently identified in human myeloid leukemias. In mice, expression of endogenous oncogenic Nras (NrasG12D/+) in hematopoietic cells leads to expansion of myeloid progenitors, increased long-term reconstitution of bone marrow cells, and a chronic myeloproliferative neoplasm (MPN). However, acute expression of NrasG12D/+ in a pure C57BL/6 background does not induce hyperactivated GM-CSF signaling or increased proliferation in myeloid progenitors. It is thus unclear how NrasG12D/+ signaling promotes leukemogenesis. Here we show that hematopoietic stem cells (HSCs) expressing NrasG12D/+ serve as MPN initiating cells. They undergo moderate hyperproliferation with increased self-renewal. The aberrant NrasG12D/+ HSC function is associated with hyperactivation of ERK1/2 in HSCs. Conversely, downregulation of MEK/ERK by pharmacological and genetic approaches attenuates the cycling of NrasG12D/+ HSCs and prevents the expansion of NrasG12D/+ HSCs and myeloid progenitors. Our data delineate critical mechanisms of oncogenic Nras signaling in HSC function and leukemogenesis. three NrasG12D/G12D HSCs samples, three NrasG12D/+ HSCs samples, two Nras+/+ HSCs control samples.
2013-05-29 | E-GEOD-46948 | biostudies-arrayexpress
Project description:Global Expression profiling of mutant mouse multipotent progenitors was performed. In order to mitigate the impact of the studied driver mutations on cell surface phenotypes, we performed transcriptome analysis on a homogeneous population of purified lineage negative, Sca-1/Kit positive multipotent progenitor cells (MPPs, cell surface profile: Lin-/CD34+/Flt3+/CD48+/CD150-). Aprroximately 1000 multipotent progenitors were isolated from wild type or mutant Npm1cA/+, NrasG12D, Npm1cA/+;NrasG12D, Flt3ITD/+ and Npm1cA/+;Flt3ITD/+ murine bone marrow cells. Total RNA extracted and mRNA amplified using
2017-07-30 | E-MTAB-5358 | biostudies-arrayexpress
Project description:Global Expression profiling of non-committed lineage negative hematopoietic progenitors was performed on bone marrow aspirates from wild type control and mutant mice. Lineage negative (lin-) bone marrow progenitors were isolated from wild type or mutant Npm1cA/+, NrasG12D, Npm1cA/+;NrasG12D using MACS Microbeads (Miltenyl Biotec).
2017-07-30 | E-MTAB-5359 | biostudies-arrayexpress
Project description:Gene expression changes in NRASG12D, NUP98-NSD1 and NUP98-NSD1+NRASG12D transformed mouse bone marrow cells (in vitro).
| PRJNA638683 | ENA
Project description:Global Gene Expression of hematopoietic stem cells expressing endogenous NrasG12D/G12D, NrasG12D/+, Nras+/+
| PRJNA203126 | ENA
Project description:Oncogenic NRAS mutations are frequently identified in human myeloid leukemias. In mice, expression of endogenous oncogenic Nras (NrasG12D/+) in hematopoietic cells leads to expansion of myeloid progenitors, increased long-term reconstitution of bone marrow cells, and a chronic myeloproliferative neoplasm (MPN). However, acute expression of NrasG12D/+ in a pure C57BL/6 background does not induce hyperactivated GM-CSF signaling or increased proliferation in myeloid progenitors. It is thus unclear how NrasG12D/+ signaling promotes leukemogenesis. Here we show that hematopoietic stem cells (HSCs) expressing NrasG12D/+ serve as MPN initiating cells. They undergo moderate hyperproliferation with increased self-renewal. The aberrant NrasG12D/+ HSC function is associated with hyperactivation of ERK1/2 in HSCs. Conversely, downregulation of MEK/ERK by pharmacological and genetic approaches attenuates the cycling of NrasG12D/+ HSCs and prevents the expansion of NrasG12D/+ HSCs and myeloid progenitors. Our data delineate critical mechanisms of oncogenic Nras signaling in HSC function and leukemogenesis.
2013-05-29 | GSE46948 | GEO
Project description:Investigation of the transcriptional profile of AML in response to DHODH inhibition by AG636. I1DN model was generated by co-transduction of foetal liver derived HSPCs with constructs encoding IDH1R132H, DNMT3AR882H and NrasG12D. Cells were transplanted into Ptprca recipients. Mice bearing I1DN tumors were treated with AG636 for one day. Leukemic stem cells (cKit high; CD11b low) from bone marrow and spleen were isolated and RNA sequencing performed.
2022-04-26 | GSE181663 | GEO
Project description:This phase II trial studies how well giving fludarabine phosphate, cyclophosphamide, tacrolimus, mycophenolate mofetil and total-body irradiation together with a donor bone marrow transplant works in treating patients with high-risk hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells by stopping them from dividing or killing them. Giving cyclophosphamide after transplant may also stop the patient’s immune system from rejecting the donor’s bone marrow stem cells. The donated stem cells may replace the patient’s immune system cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body’s normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening
| 2008483 | ecrin-mdr-crc