GEO DataSets

(Submitter supplied) We demonstrate the in vivo efficacy of the histone deacetylase inhibitor Panobinostat (LHB589) against MLL-rearranged ALL using xenograft mouse models of MLL-rearranged ALL cell lines and primary patient cells. Panobinostat monotherapy showed strong anti-leukaemic effects, extending survival and reducing overall disease burden. Comprehensive molecular analyses in vitro showed the anti-leukaemic activity in MLL-rearranged ALL to involve depletion of H2B ubiquitination via suppression of the RNF20/RNF40/WAC E3 ligase complex.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

32 Samples

Download data: CEL

(Submitter supplied) MLL-fusions are potent oncogenes that initiate aggressive forms of acute leukemia. As aberrant transcriptional regulators, MLL-fusion proteins alter gene expression in hematopoietic cells through interactions with the histone H3 lysine 79 (H3K79) methyltransferase DOT1L. Notably, interference with MLL-fusion cofactors like DOT1L is an emerging therapeutic strategy in this disease. Here we identify the histone H2B E3 ubiquitin ligase RNF20 as an additional requirement for MLL-fusion-mediated leukemogenesis. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

3 Samples

Download data: TXT

(Submitter supplied) 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.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

73 Samples

Download data: CEL

(Submitter supplied) 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.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL96

52 Samples

Download data: CEL, CHP

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL4126

60 Samples

Download data: TXT

(Submitter supplied) 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.

Organism:

Homo sapiens

Type:

Expression profiling by array

Dataset:

GDS4297

Platform:

GPL570

43 Samples

Download data: CEL

Analysis of primary MLL-rearranged ALL samples (>90% leukemic blasts) from untreated infants. In vitro prednisolone sensitivity was assessed by a 4day cytotoxicity (MTT) assay. Results provide insight into the molecular basis of glucocorticoid resistance in MLL-rearranged infant ALL patients.

Organism:

Homo sapiens

Type:

Expression profiling by array, transformed count, 2 disease state sets

Platform:

GPL570

Series:

GSE32962

43 Samples

Download data: CEL

(Submitter supplied) MLL-r infant acute lymphoblastic leukemia (ALL) has largely unclear oncogenesis. It has been shown unrelated to copy number change or mutations in the tyrosine kinome. We therefore, explored the possible role of genome wide CpG island hypermethylation in MLL-r infant ALL. We employed the HpaII-tiny fragment Enrichment by Ligation-mediated PCR (HELP) assay to examine MLL-r infant leukemia samples (n=5), other common childhood ALL (n=5) and normals (n=5). more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL6604

15 Samples

Download data: PAIR

(Submitter supplied) The hematological malignancies classified as Mixed Lineage leukemias (MLL) harbor fusions of the MLL1 gene to partners that are members of transcriptional elongation complexes. MLL-rearranged leukemias are associated with extremely poor prognosis and response to conventional therapies and efforts to identify molecular targets are urgently needed. Using mouse models of MLL-rearranged acute myeloid leukemia (AML), here we show that genetic inactivation or small molecule inhibition of the protein arginine methyltransferase PRMT5 exhibit anti-tumoral activity in MLL-fusion protein driven transformation. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

6 Samples

Download data: TXT

(Submitter supplied) Leukemias that harbor translocations involving the mixed lineage leukemia gene (MLL) possess unique biological characteristics and often have an unfavorable prognosis. Gene expression analyses demonstrate a distinct profile for MLL-rearranged leukemias with consistent high-level expression of select Homeobox genes including HOXA9. Here, we investigated the effects of HOXA9 suppression in MLL-rearranged and MLL-germline leukemias utilizing RNAi. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL571

12 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus; Homo sapiens

Type:

Expression profiling by array; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL14761 GPL13112 GPL1261

44 Samples

Download data: BW, CEL, TDF

(Submitter supplied) ZNF521 is a multiple zinc finger transcription factor previously identified because abundantly and selectively expressed in normal CD34+ hematopoietic stem and progenitor cells. From microarray datasets, aberrant expression of ZNF521 has been reported in both pediatric and adult acute myeloid leukemia (AML) patients with MLL gene rearrangements. However, a proper validation of microarray data is lacking, likewise ZNF521 contribution in MLL-rearranged AML is still uncertain. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

6 Samples

Download data: CEL

(Submitter supplied) Analysis of basal gene expression in patient-derived xenograft cells. A panel of pediatric T-, B- and MLL-ALL xenografts was utilized to further understand the biology of leukemia

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10904

31 Samples

Download data: TXT

(Submitter supplied) Gene expression upon DOT1L inhibition, or Menin inhibition, or a combination of DOT1L and Menin inhibiting agents, was assessed in several MLL-rearranged human cell lines and a mouse model of MLL-AF9 leukemia. The goal of the study was to explore the mechanisms by which the EPZ0004777 and MI-2-2 chemicals collaborate to induce differentiation and cell death in MLL-AF4 and MLL-AF9 leukemias.

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by array

Platforms:

GPL1261 GPL570

56 Samples

Download data: CEL

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

28 Samples

Download data: CEL

(Submitter supplied) Acute myeloid leukemia (AML) with chromosomal rearrangements involving the H3K4 methyltransferase mixed-lineage leukemia (MLL) is an aggressive subtype with low overall survival. MLL rearrangements rapidly transform hematological stem and progenitor cell (HSPC) to leukemia stem cell (LSC). Bortezomib (Velcade) is used widely in hematological malignancies. However, it is still unknown whether bortezomib possesses anti-self-renewal and anti-leukemogenesis of LSC in AML with MLL rearrangements. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

2 Samples

Download data: TXT, XLSX

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Xenopus laevis; Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL18936 GPL17021

33 Samples

Download data: TSV

(Submitter supplied) Genomic analyses of patients with congenital heart disease (CHD) have identified significant contribution from mutations affecting cilia genes and chromatin remodeling genes; however, the mechanism(s) connecting chromatin remodeling to CHD are unknown. Histone H2B mono-ubiquitination (H2Bub1) is catalyzed by the RNF20 complex consisting of RNF20, RNF40 and UBE2B. Here, we show significant enrichment of loss-of-function mutations affecting H2Bub1 in CHD patients (enrichment=6.01, p=1.67x10-03), some of whom had abnormal laterality associated with cilia dysfunction. more...

Organism:

Xenopus laevis

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18936

25 Samples

Download data: TSV, TXT

(Submitter supplied) Genomic analyses of patients with congenital heart disease (CHD) have identified significant contribution from mutations affecting cilia genes and chromatin remodeling genes; however, the mechanism(s) connecting chromatin remodeling to CHD are unknown. Histone H2B mono-ubiquitination (H2Bub1) is catalyzed by the RNF20 complex consisting of RNF20, RNF40 and UBE2B. Here, we show significant enrichment of loss-of-function mutations affecting H2Bub1 in CHD patients (enrichment=6.01, p=1.67x10-03), some of whom had abnormal laterality associated with cilia dysfunction. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17021

8 Samples

Download data: BW

(Submitter supplied) Purpose: The chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene have been extensively characterized as a potent oncogenic driver on the molecular and mechanistic level in acute lymphoblastic (ALL) and acute myeloid (AML) leukemia. For its oncogenic function the MLL fusion protein is hijacking the the multi enzyme super elongation complex (SEC) leading to elevated expression of MLL target genes (e.g. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

305 Samples

Download data: TSV