Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA146413 | ENA |
REPOSITORIES: ENA
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Project description:Acute Lymphoblastic Leukemia (ALL) in infants (<1 year of age) is characterized by a high incidence of MLL translocations which is associated with a poor prognosis. Contributing to this poor prognosis is cellular drug resistance, especially to glucocorticoids like prednisolone. Although in vitro prednisolone resistance mechanisms have been proposed in pediatric ALL, it has never been studied in MLL-rearranged infant ALL, which are highly resistant to glucocorticoids in vitro and in vivo. We analyzed primary MLL-rearranged infant ALL expression profiles, which were either in vitro prednisolone-resistant or prednisolone-sensitive, in order to study in vitro prednisolone resistance.
2011-10-12 | E-GEOD-32962 | biostudies-arrayexpress
Project description:Acute Lymphoblastic Leukemia (ALL) in infants (<1 year of age) is characterized by a high incidence of MLL translocations which is associated with a poor prognosis. Contributing to this poor prognosis is cellular drug resistance, especially to glucocorticoids like prednisolone. Although in vitro prednisolone resistance mechanisms have been proposed in pediatric ALL, it has never been studied in MLL-rearranged infant ALL, which are highly resistant to glucocorticoids in vitro and in vivo.
2011-10-13 | GSE32962 | GEO
Project description:Although the prognosis for childhood Acute Lymphoblastic Leukemia (ALL) in general has improved tremendously over the last decades, the survival chances for infants (<1 year of age) with ALL remains poor. A major obstacle hampering successful treatment results in infant ALL is cellular resistance to several drugs currently used in the treatment of ALL, especially to prednisolone (or prednisone). Therefore we set out to search for genes differentially expressed between from infant (children <1 year of age) and non-infant (children >1 year of age) ALL samples either resistant or sensitive to prednisolone. The in vitro prednisolone response in primary infant and non-infant ALL samples was determined by 4-day cytotoxicity (MTT) assays. Patient samples were characterized as either sensitive or resistant based on the LC50 value (i.e. the concentration of prednisolone lethal to 50% of the leukemic cells). Prednisolone sensitivity was defined by LC50 values <0.1 ug/mL prednisolone, and prednisolone resistance by LC50 values >150 ug/mL. Samples showing intermediate in vitro prednisolone responses were excluded. In total 25 infant (<1 year of age) and 27 non-infant (>1 year of age) ALL samples were selected for RNA extraction and hybridization on Affymetrix HU133A microarrays. The obtained gene expression signatures were used to identify gene differentially expressed between prednisolone resistant and sensitive patients, in order to gain insights into the mechanism(s) underlying prednisolone resistance in infant and non-infant ALL.
2009-12-15 | E-GEOD-19143 | biostudies-arrayexpress
Project description:The aggressive MLL-rearranged leukemias are well-known for their unique gene-expression profiles. The goal of this study was to characterize the MLL-specific DNA methylation profiles in infant acute lymphoblastic leukemia (ALL). Genome-wide DNA methylation profiling was performed on primary infant ALL samples. The majority of infant ALL samples demonstrated severe DNA hypermethylation compared with normal pediatric bone marrows, which implies that targeting of DNA methylation may be an interesting option for future therapeutic strategies in MLL-rearranged infant ALL. Using ALL cell lines carrying the MLL translocation t(4;11) (SEMK2 and RS4;11) as a model for the patient cells, we demonstrated that the hypermethylated genes are sensitive to demethylation.
2009-11-23 | GSE18400 | GEO
Project description:Infant and adult MLL-rearranged (MLLr) leukemia represents a disease with few treatment options and a dismal prognosis. Here, we present an in-depth proteomic characterization of in utero-initiated and adult-onset MLLr leukemia in a mouse model of MLL-ENL-mediated leukemogenesis. We characterize early proteomic events of MLL-ENL-mediated transformation in fetal and adult progenitors.
2024-04-02 | PXD042249 | Pride
Project description:Acute Lymphoblastic Leukemia (ALL) in infants (<1 year) is characterized by a poor prognosis and a high incidence of MLL translocations. Several studies demonstrated the unique gene expression profile associated with MLL-rearranged ALL, but generally small cohorts were analyzed as uniform patient groups regardless of the type of MLL translocation, while the analysis of translocation-negative infant ALL remained unacknowledged. We generated and analyzed primary infant ALL expression profiles (n=73) typified by translocations t(4;11), t(11;19) and t(9;11), or the absence of MLL translocations, in order to study translocation-specific gene expression between the different genetic subtypes of infant ALL.
2009-12-15 | E-GEOD-19475 | biostudies-arrayexpress
Project description:Extensive molecular and prognostic characterization of wild-type MLL infant ALL. Background: Approximately 20% of all infant ALL cases carry wild-type (or germline) MLL genes. To date, wild-type MLL infant ALL patients are generally regarded as young pediatric precursor B-ALL patients, but extensive characterization of this specific patient group largely remains unacknowledged. Methods: We here studied a relatively large cohort of 78 wild-type MLL infant ALL samples, using clinical parameters, array-comparative genomic hybridization analysis, gene expression profiling, multiplex ligation-dependent probe amplification, and conventional sequencing. Findings: Wild-type MLL infant ALL patients are generally characterized by a lower incidence of favourable prognostic factors than pediatric (non-infant) B-ALL patients, and patients at high risk of therapy failure typically display an immature pro-B immunophenotype or respond poorly to prednisone. Using gene expression profiling, we found MEIS1 expression to additionally be highly predictive for clinical outcome in wild-type MLL infant ALL with a favourable prognosis in the wild-type MLL infants with low MEIS1 expression (DFS 88%% versus 50%, p=0•01). Overall the incidence of DNA copy number variations and genetic abnormalities in genes involved in B-cell differentiation is lower in wild-type MLL infant ALL patients as compared with pediatric precursor B-ALL patients. Interpretation: Wild-type MLL infant ALL represents a highly heterogeneous patient group, which cannot be unified by one or a few known recurrent genomic aberrations. High-level MEIS1 expression and an immature pro-B immunophenotype in high-risk wild-type MLL infant ALL patients shows parallel with the unfavourable prognosis of MLL-rearranged infant ALL patients. In contrast, wild-type MLL infant ALL patients expressing lower levels of MEIS1 and displaying more differentiated (pre-B or common) phenotypes may well be more related to pediatric precursor B-ALL patients older than 1 year of age. We advocate that a treatment strategy in wild-type MLL infant ALL based on MEIS1 expression could be beneficial for improving survival. Gene expression profiling of wild-type MLL infant ALL. Additional wild-type MLL infant ALL patient samples (n=17) to the earlier samples published under GSE19475 (GSM485309 to GSM485322).
2014-10-01 | E-GEOD-58565 | biostudies-arrayexpress
Project description:We investigated the anti-leukemic effects of the Bromodomain and Extra Terminal inhibitor I-BET151 on primary MLL-AF4 patient samples, using a xenotransplantation mouse model of MLL+ infant ALL in vivo. We reported that I-BET151 treatment impairs the engraftment and the disease burden of primary MLL+ infant ALL samples transplanted into immunedeficient mice. I-BET151 is able to arrest the growth of leukemic cells by blocking cell division and rapidly inducing apoptosis, through the deregulation of crucial target genes of the BRD4 and HOXA9/HOXA7 network. Moreover I-BET151 sensitizes glucocorticoid-resistant MLL+ cells to Prednisolone. Finally we observed that I-BET151 treatment is even more efficient when used in combination with HDAC inhibitor.
2018-05-11 | GSE79057 | GEO
Project description:Acute Lymphoblastic Leukemia (ALL) in infants (<1 year) is characterized by a poor prognosis and a high incidence of MLL translocations. Several studies demonstrated the unique gene expression profile associated with MLL-rearranged ALL, but generally small cohorts were analyzed as uniform patient groups regardless of the type of MLL translocation, while the analysis of translocation-negative infant ALL remained unacknowledged.
2009-12-16 | GSE19475 | GEO
Project description:Although the prognosis for childhood Acute Lymphoblastic Leukemia (ALL) in general has improved tremendously over the last decades, the survival chances for infants (<1 year of age) with ALL remains poor. A major obstacle hampering successful treatment results in infant ALL is cellular resistance to several drugs currently used in the treatment of ALL, especially to prednisolone (or prednisone). Therefore we set out to search for genes differentially expressed between from infant (children <1 year of age) and non-infant (children >1 year of age) ALL samples either resistant or sensitive to prednisolone.
2009-12-16 | GSE19143 | GEO