GEO DataSets

(Submitter supplied) The RNA splicing factor SF3B1 is recurrently mutated in chronic lymphocytic leukemia (CLL), but its functional role in the pathogenesis of this disease has not been firmly established. Here, we show that conditional expression of heterozygous Sf3b1-K700E mutation in mouse B lineage cells disrupts pre-mRNA splicing, alters B-cell development and function, and induces a state of cellular senescence. B-cell restricted expression of this mutation combined with Atm deletion led to the overcoming of cellular senescence, together with enhanced genome instability and the development of clonal B220+CD5+ CLL cells in elderly mice at low penetrance. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL9185

17 Samples

Download data: XLSX

(Submitter supplied) RNA splicing factor SF3B1 is recurrently mutated in various cancers, particularly in hematological malig-nancies. We previously reported that co-expression of Sf3b1 mutation and Atm deletion in B cells, but not either lesion alone, leads to the onset of chronic lymphocytic leukemia (CLL) with CLL cells harboring chromosome amplification. However, the exact role of Sf3b1 mutation and Atm deletion in chromosomal instability (CIN) remains unclear. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL11154

14 Samples

Download data: NARROWPEAK, TXT

(Submitter supplied) We performed RRBS and WGBS on primary human chronic lymphocytic leukemia and normal healthy donor B cell samples Due to patient privacy concerns, the raw data is being made available via controlled access in dbGaP (http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000435.v1.p1).

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL11154

149 Samples

Download data: TXT

(Submitter supplied) Mutations of SF3B1 in CLL induce alternative splicing in multiple transcripts, including DVL2. DVL2 in turn can act as a negative regulator of NOTCH1 signaling. Gene Expression Profile (GEP) was used to investigate the activation of the NOTCH1 pathway in presence of alternatively spliced DVL2.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL17077

28 Samples

Download data: TXT

(Submitter supplied) To analyze expression differences between Trp53 pro-and deficient as well as Atm pro- and deficient murine CLL tumors developing in the Eµ-TCL1 mouse model, we analyzed splenocytes isolated from heavily infiltrated spleens of sick mice. To investigate differences in the response to cyclophosphamide, we also analyzed splenocytes from leukemic animals that were isolated twelve hours after intraperitoneal injection of cyclophosphamide.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL18802

17 Samples

Download data: CEL

(Submitter supplied) Although somatic mutations in the DNA methyltransferase 3A (DNMT3A) in chronic lymphocytic leukemia (CLL) are rare, DNMT3A transcript and protein expression is frequently reduced in CLL patients, and previous studies have associated low DNMT3A expression with more aggressive disease and poorer survival.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

24 Samples

Download data: TXT

(Submitter supplied) Chronic lymphocytic leukemia (CLL) cell survival and growth is fueled by aberrant activation of various pro-survival signaling pathways within tumor niches. Specifically, B-cell receptor (BCR) signaling, toll-like receptor signaling, and supportive cellular interactions drive constitutive activation of NF-κB signaling and transcription of proliferative/pro-survival genes. Directly targeting the NF-κB pathway has been a challenge, however, herein, we investigated SpiD3, a spirocyclic dimer and novel NF-κB pathway inhibitor in preclinical models of CLL. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21697

9 Samples

Download data: XLSX

(Submitter supplied) Using RNA-Seq, we determined changes to gene expression and splicing on inducible expression of SF3B1-WT and SF3B1-MUT (K700E) in K562 cells.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL15520

8 Samples

Download data: GTF

(Submitter supplied) Inactivating mutations in the NF-kB inhibitor NFKBIE are frequent in chronic lymphocytic leukemia (CLL) and have been associated with accelerated disease progression and inferior responses to chemotherapy. To further understand the role of NFKBIE mutations in CLL, we disrupted by CRISPR/Cas9 editing the NFKBIE gene in CLL cells derived from the Eμ-TCL1 transgenic mouse model and investigated how this will affect CLL growth and response to B cell receptor inhibitor treatment. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

22 Samples

Download data: TXT

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

Organism:

Homo sapiens

Type:

Non-coding RNA profiling by array; Expression profiling by array

Platforms:

GPL8227 GPL6244

471 Samples

Download data: CEL, TXT

(Submitter supplied) Highly homologous B-cell receptors, stereotyped BCR, are expressed in a recurrent fraction of patients with chronic lymphocytic leukemia (CLL). In this study, we investigated the biological and molecular features of leukemic cells from 16 patients utilizing stereotyped subset #4 BCR (IGHV4-34) in a prospective cohort of 462 Binet stage A CLL patients. All subset #4 patients were characterized by the IGHV mutated gene configuration and by the absence of unfavorable cytogenetic lesions, and NOTCH1 and SF3B1 mutations. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

229 Samples

Download data: CEL

(Submitter supplied) Highly homologous B-cell receptors, stereotyped BCR, are expressed in a recurrent fraction of patients with chronic lymphocytic leukemia (CLL). In this study, we investigated the biological and molecular features of leukemic cells from 16 patients utilizing stereotyped subset #4 BCR (IGHV4-34) in a prospective cohort of 462 Binet stage A CLL patients. All subset #4 patients were characterized by the IGHV mutated gene configuration and by the absence of unfavorable cytogenetic lesions, and NOTCH1 and SF3B1 mutations. more...

Organism:

Homo sapiens

Type:

Non-coding RNA profiling by array

Platform:

GPL8227

242 Samples

Download data: TXT

(Submitter supplied) The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has substantially improved therapeutic options for chronic lymphocytic leukemia (CLL). Although ibrutinib is not curative, it has a profound effect on CLL cells and may create new pharmacologically exploitable vulnerabilities. To identify such vulnerabilities, we developed a systematic approach that combines epigenome profiling (charting the gene-regulatory basis of cell state) with single-cell chemosensitivity profiling (quantifying cell-type-specific drug response) and bioinformatic data integration. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL20301

38 Samples

Download data: BIGWIG, CSV, NARROWPEAK

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

Organism:

Homo sapiens

Type:

Expression profiling by array; Non-coding RNA profiling by array

Platforms:

GPL8227 GPL6244

310 Samples

Download data: CEL, TXT

(Submitter supplied) Prospective series of 136 clinical monoclonal B lymphocytosis (cMBL) and 216 chronic lymphocytic leukemia (CLL) Rai 0 patients, were investigated in this study. While the distribution of CD38 and ZAP-70 positivity was similar, IGHV-mutated cases were more frequent among cMBL (P = 0.005). A Cox multivariate analysis on the whole patient cohort showed that cMBL condition was predictive of longer PFS, while CD38 expression and IGHV-unmutated status and CD38 expression correlated significantly with a shorter PFS in cMBL and Rai0-CLL, respectively. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

160 Samples

Download data: CEL

(Submitter supplied) Prospective series of 136 clinical monoclonal B lymphocytosis (cMBL) and 216 chronic lymphocytic leukemia (CLL) Rai 0 patients, were investigated in this study. While the distribution of CD38 and ZAP-70 positivity was similar, IGHV-mutated cases were more frequent among cMBL (P = 0.005). A Cox multivariate analysis on the whole patient cohort showed that cMBL condition was predictive of longer PFS, while CD38 expression and IGHV-unmutated status and CD38 expression correlated significantly with a shorter PFS in cMBL and Rai0-CLL, respectively. more...

Organism:

Homo sapiens

Type:

Non-coding RNA profiling by array

Platform:

GPL8227

150 Samples

Download data: TXT

(Submitter supplied) We established a mouse model of KrasG12D, Trp53-/- and Sf3b1-K700E murine pancreatic cancer to elucidate the impact of the SF3B1 mutation found in human PDAC on the KPC mouse model.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

7 Samples

Download data: XLSX

(Submitter supplied) Chronic Lymphocytic Leukaemia (CLL) is the most common leukemia in adults in the Western world. B cell receptor (BCR) signalling is known to be crucial for the pathogenesis and maintenance of CLL cells develop from mature CD5+ B cells. BCR signalling is regulated by the inhibitory co-receptor Siglec-G and Siglec-G-deficient mice have an enlarged CD5+ B1a cell population. Here, we determine how Siglec-G expression influences the severity of CLL.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16417

121 Samples

Download data: FASTA, TSV

(Submitter supplied) Richter’s syndrome (RS) is an aggressive B-cell lymphoma arising from chronic lymphocytic leukemia (CLL). RS patients are generally unresponsive both to conventional and B-cell receptor-targeted agents such as ibrutinib. Mouse models that mimic the biology and therapeutic response of RS are lacking, which hampers the development of alternative treatment strategies urgently needed to improve the dismal outcome of RS patients. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

9 Samples

Download data: TSV

(Submitter supplied) We have analyzed 2 normal B cells isolated from peripheral blood and 5 CLL specimens with affy 133A microarray for expression. We used microarrays to analyze gene expression in normal B cells and CLL cells.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL96

7 Samples

Download data: CEL, CHP