Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA388676 | ENA |
REPOSITORIES: ENA
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Project description:The human acute myeloid leukemia cell lines MOLM-14 and THP-1 were silenced for MUC1 expression by lentiviral transduction of MUC1 specific shRNA or scrambled control. RNA was extracted and NanoString array for microRNAs was performed.
2017-06-01 | GSE99510 | GEO
Project description:Gene expression data from AML cell lines, MOLM-14, U937, THP-1 and HL-60, that were infected with a scrambled control hairpin (shControl), two shRNAs directed against GSK-3B (shGSK3B_1 and shGSK3B_2), or two shRNAs directed against GSK-3A (shGSK3A_5 and shGSK3A_6). Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Long-term survival of patients with AML has changed little over the past decade, necessitating the identification and validation of new AML targets. Integration of genomic approaches with small-molecule and genetic-based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. Here, we identified a role for glycogen synthase kinase 3A (GSK-3A) in AML by performing two independent small-molecule library screens and an shRNA screen for perturbations that induced a differentiation expression signature in AML cells. GSK-3 is a serine-threonine kinase involved in diverse cellular processes including differentiation, signal transduction, cell cycle regulation, and proliferation. We demonstrated that specific loss of GSK-3A induced differentiation in AML by multiple measurements, including induction of gene expression signatures, morphological changes, and cell surface markers consistent with myeloid maturation. GSK-3AM-bM-^@M-^Sspecific suppression also led to impaired growth and proliferation in vitro, induction of apoptosis, loss of colony formation in methylcellulose, and anti-AML activity in vivo. Although the role of GSK-3B has been well studied in cancer development, these studies support a role for GSK-3A in AML. The AML cell lines, MOLM-14, U937, THP-1 and HL-60, were infected with a scrambled control hairpin (shControl), two shRNAs directed against GSK-3B (shGSK3B_1 and shGSK3B_2), and two shRNAs directed against GSK-3A (shGSK3A_5 and shGSK3A_6).
2012-02-27 | E-GEOD-35200 | biostudies-arrayexpress
Project description:Effect of HOXA9 shRNA versus DB1055 treatment of human THP-1 AML cell line
2020-11-13 | GSE106831 | GEO
Project description:Acute myeloid leukemia (AML) is a clonal hematopoietic malignancy, characterized by expansion of immature leukemic blasts in the bone marrow. In AML, specific tyrosine kinases have been implicated in leukemogenesis, and are associated with poor treatment outcome. However, targeted therapy using kinase inhibitors (KIs) has had limited success, and may be improved by proper patient selection. We performed phosphotyrosine (pY) based, label-free phosphoproteomics to identify hyperphosphorylated, active kinases in AML cell lines as targets and predictive biomarkers to select KIs for treatment. We identified 3605 class I phosphorylation sites in 16 AML cell lines (EOL-1, KG-1a, MM6, KG-1, ME-1, NB-4, Kasumi-3, MV4-11, THP-1, HEL, HL-60, Kasumi-1, Kasumi-6, ML-2, OCI-AML3, MOLM-13) that exhibited large variation in the number and level of phosphopeptides per cell line (241-2764). Ranking analyses successfully pinpointed the hyperactive kinases PDGFRA, FGFR1, KIT, and FLT3 in eight cell lines with a corresponding kinase mutation. Additionally, we identified unexpected drivers in two more cell lines (PDGFRA in Kasumi-3 and FLT3 in MM6) which proved sensitive to specific kinase inhibitors. Six cell lines without a clear receptor tyrosine kinase (RTK) driver showed evidence of MAPK1/3 activation, consistent with the presence of activating RAS mutations. Our data show the potential of pY phosphoproteomics to identify key drivers in AML cells, and the predictive value of the phosphoproteome profiles in TKi selection for targeted treatment.
2019-11-11 | PXD007237 | Pride
Project description:EVI1 is one of the famous poor prognostic markers for a chemotherapy-resistant acute myeloid leukemia (AML). To identify molecular targets on the surface of leukemia cells with EVI1high expression, we compared the gene expression profiles of several AML cell lines by DNA microarray To search for novel molecular targets in refractory myeloid leukemia with high EVI1 expression, we initially analyzed the gene expression profiles of 12 human myeloid cell lines. Four cell lines with chromosome 3q26 abnormalities (UCSD/AML1, HNT-34, Kasumi-3 and MOLM-1) expressed EVI1High, and eight myeloid cell lines without chromosome 3q26 abnormalities (HEL, HL-60, K052, THP-1, FKH-1, K051, NH and OIH-1) expressed low levels of EVI1 (EVI1Low)
2012-01-18 | E-GEOD-35159 | biostudies-arrayexpress
Project description:The objective of the sudy is to explore the biological pathways controlled by Pim2 in FLT3-ITD positive AML We used microarrays to investigate gene expression in the MOLM-14 AML cell line in which Pim2 knockdown was induced by RNA interference (doxycycline-inducible shRNA)
2018-02-14 | GSE94870 | GEO
Project description:As a direct consequence of the high diversity of the aggressive blood cancer acute myeloid leukemia (AML), proteomic samples from patients are strongly heterogeneous, rendering their accurate relative quantification challenging. In the present study, we investigated the benefits of using a super-SILAC mix of AML derived cell lines as internal standard for quantitative shotgun studies. The Molm-13, NB4, MV4-11, THP-1, and OCI-AML3 cell lines were selected for their complementarity with regard to clinical, cytogenetic and molecular risk factors used for prognostication of AML patients. The resulting internal standard presents a high coverage of the AML proteome compared to single cell lines allied with high technical reproducibility, thus enabling its use for AML patient comparison. This was confirmed by comparing the protein regulation between the five cell lines and applying the internal standard to patient material.
2014-07-15 | PXD000441 | Pride
Project description:Acute myeloid leukemia (AML) with the FLT3 internal tandem duplication (FLT3-ITD AML) accounts for 20-30% of AML cases. This subtype usually responds poorly to conventional therapies including FLT3 tyrosine kinase inhibitors (TKIs) due to molecular bypass mechanisms. New therapeutic strategies are therefore urgently needed. Pim kinases are FLT3-ITD oncogenic targets that have been implicated in FLT3 TKI resistance. However, their precise biological function downstream of FLT3-ITD requires further investigation. MOLM-14 is a human FLT3-ITD AML cell line that was transduced with control (scrambled) or anti-Pim2 shRNA using lentivirus. Expression of hairpins was induced by doxycycline during 3 days and the experiments were done in biological triplicates. One million of MOLM-14 shSCR or shPim2 cells were lysed in 200µl lysis buffer (50 mM Tris (pH 8.5), 2% SDS, 20 mM TCEP, 50 mM chloroacetamide) and heated 5 min at 95°C. Proteins (50µg) from whole cell lysate were trypsin-digested overnight using the filtered-aided sample preparation (FASP) method. Liquid chromatography and mass spectrometry analyses were performed on anU3000 RSLC nanoflow-HPLC system coupled to a Q-Exactive Orbitrap mass spectrometer (both from Thermo Fisher Scientific). The analyses of raw data were performed by LFQ on Maxquant software with a maximum of 1% FDR and match between runs enabled within a 0.7 min match time window and 20 min alignment time window. Maxquant LFQ data were analyzed with Perseus, Ingenuity and Excel softwares.
2017-09-18 | PXD005880 | Pride
Project description:We used an in vivo short hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo, and for human leukemia cells in xenotransplantation studies.M-BM- In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase, Syk.M-BM- In contrast, loss of Itgb3 in normal HSPCs did not affect engraftment, reconstitution, or differentiation. M-BM- Finally, we confirmed that Itgb3 is dispensable for normal hematopoiesis and required for leukemogenesis using an Itgb3 knockout mouse model.M-BM- Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML. R940406 (R406, the active metabolite of fostamatinib) was supplied by Rigel Pharmaceuticals, Inc., South San Francisco, CA, and AstraZeneca Pharmaceuticals, Wilmington, DE, USA. R406 was resuspended in dimethyl sulfoxide (DMSO) (Sigma-Aldrich) and stored at M-bM-^HM-^R80M-BM-0C. . HL-60, U937 and KG-1 cell lines were purchased from the American Type Culture Collection. MOLM-14 cell lines were provided by Dr. Scott Amstrong (Dana-Farber Cancer Institute, Boston MA, USA.) All cell lines were maintained in RPMI 1640 (Cellgro) supplemented with 1% penicillin-streptomycin and 10% fetal bovine serum (FBS, Sigma-Aldrich) at 37 M-BM-0C with 5% CO2. MOLM-14, U937, HL-60 and KG-1 cells were grown in 4mM R406 for 24 hours
2013-04-24 | E-GEOD-46302 | biostudies-arrayexpress
Project description:Gene expression data from AML cell lines, MOLM-14, U937, THP-1 and HL-60, that were infected with a scrambled control hairpin (shControl), two shRNAs directed against GSK-3B (shGSK3B_1 and shGSK3B_2), or two shRNAs directed against GSK-3A (shGSK3A_5 and shGSK3A_6). Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Long-term survival of patients with AML has changed little over the past decade, necessitating the identification and validation of new AML targets. Integration of genomic approaches with small-molecule and genetic-based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. Here, we identified a role for glycogen synthase kinase 3A (GSK-3A) in AML by performing two independent small-molecule library screens and an shRNA screen for perturbations that induced a differentiation expression signature in AML cells. GSK-3 is a serine-threonine kinase involved in diverse cellular processes including differentiation, signal transduction, cell cycle regulation, and proliferation. We demonstrated that specific loss of GSK-3A induced differentiation in AML by multiple measurements, including induction of gene expression signatures, morphological changes, and cell surface markers consistent with myeloid maturation. GSK-3A–specific suppression also led to impaired growth and proliferation in vitro, induction of apoptosis, loss of colony formation in methylcellulose, and anti-AML activity in vivo. Although the role of GSK-3B has been well studied in cancer development, these studies support a role for GSK-3A in AML.
2012-02-27 | GSE35200 | GEO