H3K27 tri-methylation signature in CML CD34+ cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE188241 | GEO | 2021/11/08
REPOSITORIES: GEO
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Project description:H3K27 tri-methylation signature in CML CD34+ cells
| PRJNA777969 | ENA
Project description:Chronic myeloid leukaemia (CML) is a clonal haemopoietic stem cell (HSC) disorder associated with the BCR-ABL oncogene, which encodes a constitutively active tyrosine kinase. We have demonstrated the existence of CML HSC which are resistant to the tyrosine kinase inhibitors (TKI). We have hypothesised that CML stem cells are dependent on key survival pathways that are induced by TKI treatment. In order to elucidate these key survival pathways, we have investigated the transcriptional differences between normal and CML stem/progenitor cells (CD34+38-) and by carrying out RNA profiling for the different populations. CD34+38- cells were isolated from chronic phase patient samples. LCSciences human miRNA microarray chips were used (100% coverage of mature miRNAs listed in miRBase version 14).
2018-01-12 | E-MTAB-3220 | biostudies-arrayexpress
Project description:A characteristic of chronic phase CML is accumulation of mature cells in the peripheral blood. It has not been determined if this expansion is explained by the CD34+ cell subset composition. We conducted flowcytometry-based cell sorting to assess the CD34+ subset composition and to retrieve the respective cells. We found a significant increase in the proportion of MEP and a decrease of HSC and GMP in patients with chronic phase CML compared to their healthy counterparts. The absolute number of HSC was similar, whereas CMP, GMP and MEP were expanded 2.8- to 7.7-fold. Gene expression analysis of CD34+ cell subsets showed, that in contrast to the normal developmental hierachy, CML HSC have a transcriptional profile which is similar to CML progenitor subsets and healthy CMP. HSC in healthy individuals show greater distance to their more mature progeny within the developmental hierarchy. As the differences between CML and healthy controls were minor at the progenitor level, we focused on the further characterization of CML HSC. 614 genes were differentially expressed, including downregulation of genes involved in adhesion and migration, regulation of the stem cell pool, and differentiation. We also found abrogation of nuclear receptors NR4A1 and NR4A3, and decreased expression of c-Jun and JunB. Re-expression of c-Jun and JunB in CD34+ cells from CML patients was achieved by co-transfection of NR4A1 and NR4A3. Moreover, we functionally corroborated a decreased adhesion capacity of the CML HSC. Taken together, these findings help to explain the hematological phenotype of CML patients in chronic phase. Experiment Overall Design: CD34+ subsets of 6 patients with chronic phase CML and 5 healthy volunteers were analysed by means of gene expression profiling with the Affymetrix HU-133A 2.0 array
2009-01-13 | E-GEOD-11889 | biostudies-arrayexpress
Project description:Chronic myeloid leukaemia (CML) is a clonal haemopoietic stem cell (HSC) disorder associated with the BCR-ABL oncogene, which encodes a constitutively active tyrosine kinase. We have demonstrated the existence of CML HSC which are resistant to the tyrosine kinase inhibitors (TKI). We have hypothesised that CML stem cells are dependent on key survival pathways that are induced by TKI treatment. In order to elucidate these key survival pathways, we have investigated the transcriptional differences between CML stem/progenitor cells (CD34+38-) treated with TKIs (imatinib, dasatinib and nilotinib) at different time points (8 hours and 7 days, in the absence of growth factors) and by carrying out RNA profiling for the different populations. CD34+38- cells were isolated from chronic phase patient samples. >100ng of total RNA was amplified prior to analysis that was carried out with Affymetrix Human Gene 1.0 ST array.
2018-01-20 | E-MTAB-2594 | biostudies-arrayexpress
Project description:We analysed genome wide DNA methylation of mature (CD34-CD15+) and immature (CD34+CD15-) hematopoietic cells from patients with chronic phase CML at diagnosis. before any treatment. and compared it to their counterpart cells isolated from healthy donors.
2018-03-30 | GSE106600 | GEO
Project description:Analysis of lin-CD34+CD45+ (iCD34+) cell population from two normal bone marrow-derived (BM1K and BM9) iPSCs and two CML (CML15 and CML17) iPSCs . CML iCD34+ cells have characteristics similar to primary CML leukemia stem cell in patients. Results provide insight into molecular profile characterized CML iCD34 and mechanism of its maintenance and drug resistance. iCD34+ cell samples obtained from two control BM1K and BM9 iPSCs (both for the same normal donor) and CML15 and CML17 iPSCs (both from the same patient in chronic phase of CML). Each group was treated with DMSO (control) or 5 μM imatinib. The complete phenotype for iCD34+ cells: lin-CD34+CD45+CD90+CD117+CD45RA-. This population also inclyde Rhodaminelow and ALDKhigh cells.
2014-08-31 | E-GEOD-60065 | biostudies-arrayexpress
Project description:Comparison of gene expression profiles of CD34+ hematopoietic stem and progenitor cells from bone marrow of patients with untreated chronic myelogenous leukemia (CML) in chronic phase with those from bone marrow of healthy volunteers. Chronic myelogenous leukaemia (CML) is a malignant disorder of the hematopoietic stem cell, which is characterized by the reciprocal translocation between chromosomes 9 and 22 (t(9;22)(q34;q11)) The translocation results in the formation of the BCR-ABL fusion oncogene encoding a protein with constitutive activated tyrosine kinase activity which plays a central role in the pathogenesis of the disease. There are still several open questions with respect to BCR-ABL-induced malignant transformation. A large limitation of the existing data about BCR-ABL effects is that they are derived to a great proportion from human hematopoietic cell lines, BCR-ABL-transformed murine cell lines or fibroblasts and mouse models, which might not be representative for chronic phase CML. A suitable cell population for studies on CML biology are primary hematopoietic stem and progenitor cells from patients with CML. Therefore, we provide in this study a genome-wide expression signature of highly enriched CD34+ cells from bone marrow (BM) of untreated patients with CML in chronic phase. Gene expression profiles of immunomagnetically enriched BM CML CD34+ cells (n=9) were compared with those of normal BM CD34+ cells (n=8) using microarrays covering 8.746 genes. Total RNA was extracted, reversely transcribed, in vitro transcribed and labelled and hybridized to Affymetrix HG Focus Arrays. Following quality control and normalization differentially expressed genes were identified by significance analysis of microarrays (SAM). Comparing both groups 918 genes were significantly differentially expressed (q value <0.1%; fold change > 1.3). Several of the BCR-ABL-induced effects described in cell lines and BCR-ABL-transduced cells could also be found in primary CML progenitor cells as for example the transcriptional activation of the classical MAPK pathway and the PI3 kinase/AKT pathway and the down-regulation of the pro-apoptotic gene IRF8. Moreover, novel transcriptional changes in comparison with normal CD34+ cells were identified. These include an up-regulation of components of the TGFb signalling pathway and the non-canonical Wnt/Ca2+ pathway, a transcriptional activation of fetal haemoglobin genes and genes associated with early hematopoietic stem cells (HSC) such as HoxA9 and MEIS1 and up-regulation of genes involved in fatty acid metabolism, of the thrombin receptor PAR1 and the neuroepithelial cell transforming gene 1. Differential expression of differentiation-associated genes suggested an alteration of the composition of the CD34+ cell population in CML. This was confirmed by immunophenotypical subset analyses of chronic phase CML CD34+ cells showing an increase of erythroid progenitors and a decrease of granulocyte-macrophage progenitor cells while the proportion of HSC was similar in normal and CML CD34+ cells. In conclusion, our results give novel insights into the biology of CML hematopoietic stem and progenitor cells and could be the basis for identification of new targets for therapy.
2007-11-01 | E-GEOD-5550 | biostudies-arrayexpress
Project description:Imatinib has become the current standard therapy for patients with chronic myelogenous leukaemia (CML). For a better understanding of the Imatinib-related molecular effects in vivo, we assessed gene expression profiles of Philadelphia Chromosome positive (Ph+) CD34+ cells from peripheral blood of 6 patients with de novo CML in chronic phase. After 7 days of treatment with Imatinib the Ph+ CD34+ cells were reassessed to look for changes in the transcriptome. The expression level of 303 genes was significantly different comparing the transcriptome of the Ph+ CD34+ cells before and after 7 days of Imatinib therapy (183 down-regulated, 120 up-regulated, lower bound â¥1.2-fold). For a substantial number of genes governing cell cycle and DNA replication, the level of expression significantly decreased (CDC2, RRM2, PCNA, MCM4). On the other hand, therapy with Imatinib was associated with an increase of genes related to adhesive interactions, such as L-selectin or CD44. A group of 8 genes with differential expression levels were confirmed using a gene specific quantitative real-time PCR. Thus, during the first week of treatment, Imatinib is preferentially counteracting the bcr-abl induced effects related to a disturbed cell cycle and defective adhesion of leukemic Ph+ CD34+ cells. Experiment Overall Design: In total 6 patients with new diagnosis CML (Chronic Myelogenous Leukemia) in chronic phase are inculded in the study. The gene expression profiles of the CD34+ hematopoietic stem and progenitor cells from the patients before first treatment with Glivec (Imatinib) are compared to the gene expression profiles of the CD34+ hematopoietic stem and progenitor cells of the same patients after 7 days of treatment with 400 mg Glivec / day.
2008-10-21 | E-GEOD-12211 | biostudies-arrayexpress
Project description:Chronic myelogenous leukaemia (CML) is a malignant disorder of the hematopoietic stem cell, which is characterized by the reciprocal translocation between chromosomes 9 and 22 (t(9;22)(q34;q11)) The translocation results in the formation of the BCR-ABL fusion oncogene encoding a protein with constitutive activated tyrosine kinase activity which plays a central role in the pathogenesis of the disease. There are still several open questions with respect to BCR-ABL-induced malignant transformation. A large limitation of the existing data about BCR-ABL effects is that they are derived to a great proportion from human hematopoietic cell lines, BCR-ABL-transformed murine cell lines or fibroblasts and mouse models, which might not be representative for chronic phase CML. A suitable cell population for studies on CML biology are primary hematopoietic stem and progenitor cells from patients with CML. Therefore, we provide in this study a genome-wide expression signature of highly enriched CD34+ cells from bone marrow (BM) of untreated patients with CML in chronic phase. Gene expression profiles of immunomagnetically enriched BM CML CD34+ cells (n=9) were compared with those of normal BM CD34+ cells (n=8) using microarrays covering 8.746 genes. Total RNA was extracted, reversely transcribed, in vitro transcribed and labelled and hybridized to Affymetrix HG Focus Arrays. Following quality control and normalization differentially expressed genes were identified by significance analysis of microarrays (SAM). Comparing both groups 918 genes were significantly differentially expressed (q value <0.1%; fold change > 1.3). Several of the BCR-ABL-induced effects described in cell lines and BCR-ABL-transduced cells could also be found in primary CML progenitor cells as for example the transcriptional activation of the classical MAPK pathway and the PI3 kinase/AKT pathway and the down-regulation of the pro-apoptotic gene IRF8. Moreover, novel transcriptional changes in comparison with normal CD34+ cells were identified. These include an up-regulation of components of the TGFb signalling pathway and the non-canonical Wnt/Ca2+ pathway, a transcriptional activation of fetal haemoglobin genes and genes associated with early hematopoietic stem cells (HSC) such as HoxA9 and MEIS1 and up-regulation of genes involved in fatty acid metabolism, of the thrombin receptor PAR1 and the neuroepithelial cell transforming gene 1. Differential expression of differentiation-associated genes suggested an alteration of the composition of the CD34+ cell population in CML. This was confirmed by immunophenotypical subset analyses of chronic phase CML CD34+ cells showing an increase of erythroid progenitors and a decrease of granulocyte-macrophage progenitor cells while the proportion of HSC was similar in normal and CML CD34+ cells. In conclusion, our results give novel insights into the biology of CML hematopoietic stem and progenitor cells and could be the basis for identification of new targets for therapy. Keywords: ordered
2006-08-17 | GSE5550 | GEO
Project description:Profiling CD34+ BCR-ABL+ cells of CML patients in chronic phase or blast crisis to identify differentially expressed stage-specific genes.
2006-08-08 | E-MEXP-480 | biostudies-arrayexpress