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ZMYM2/FGFR1, BCR/FGFR1 or BCR/ABL1 in human cord blood CD34+ cells reveals similar but distinct gene expression profiles

ABSTRACT: The 8p11 myeloproliferative syndrome (EMS), also referred to as the stem cell leukemia/lymphoma syndrome, is a chronic myeloproliferative disorder that rapidly progresses into an acute leukemia. Molecularly, EMS is characterized by fusion of various partner genes to the FGFR1 gene, resulting in constitutive activation of the tyrosine kinase activity within FGFR1. The two most common fusion genes in human EMS are ZMYM2/FGFR1 (previously known as ZNF198/FGFR1) and BCR/FGFR1. To study the transcriptional programs becoming deregulated by the FGFR1 fusion genes, global gene expression analysis on human CD34+ cord blood cells expressing either of the fusion oncogenes ZMYM2/FGFR1 and BCR/FGFR1 was performed. As a reference gene we also included the more studied BCR/ABL1 fusion oncogene associated with chronic myeloid leukemia. We found that the 3 different fusion oncogenes had in common the upregulation of several genes involved in the JAK/STAT signalling pathway and also other sets of genes. However, the gene expression profiles were not identical, suggesting that both the tyrosine kinase containing gene and the partner gene would affect the transcription of downstream target genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE15811 | GEO | 2010/05/01

SECONDARY ACCESSION(S): PRJNA116725

REPOSITORIES: GEO

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ZMYM2/FGFR1, BCR/FGFR1 or BCR/ABL1 in human cord blood CD34+ cells reveals similar but distinct gene expression profiles

Project description:The 8p11 myeloproliferative syndrome (EMS), also referred to as the stem cell leukemia/lymphoma syndrome, is a chronic myeloproliferative disorder that rapidly progresses into an acute leukemia. Molecularly, EMS is characterized by fusion of various partner genes to the FGFR1 gene, resulting in constitutive activation of the tyrosine kinase activity within FGFR1. The two most common fusion genes in human EMS are ZMYM2/FGFR1 (previously known as ZNF198/FGFR1) and BCR/FGFR1. To study the transcriptional programs becoming deregulated by the FGFR1 fusion genes, global gene expression analysis on human CD34+ cord blood cells expressing either of the fusion oncogenes ZMYM2/FGFR1 and BCR/FGFR1 was performed. As a reference gene we also included the more studied BCR/ABL1 fusion oncogene associated with chronic myeloid leukemia. We found that the 3 different fusion oncogenes had in common the upregulation of several genes involved in the JAK/STAT signalling pathway and also other sets of genes. However, the gene expression profiles were not identical, suggesting that both the tyrosine kinase containing gene and the partner gene would affect the transcription of downstream target genes. Bicistronic retroviral murine stem cell virus (MSCV) vectors expressing ZMYM2/FGFR1, BCR/FGFR1or P210 BCR/ABL1 and GFP were used. The MIG control vector expressed GFP only. Two days post transfection of human CD34+ umbilical cord blood cells, GFP-sorted cells were collected in three biological replicates and RNA was isolated immediately. In total, 12 samples were hybridized and scanned.

2010-05-27 | E-GEOD-15811 | biostudies-arrayexpress

Expression data from ZMYM2-FGFR1-induced T-cell lymphomas in a mouse model

Project description:The ZMYM2-FGFR1 (formerly known as ZNF198-FGFR1) fusion kinase induces stem cell leukemia-lymphoma syndrome (SCLL), a hematological malignancy characterized by rapid transformation to acute myeloid leukemia and T-lymphoblastic lymphoma. We previously developed a mouse model of ZMYM2-FGFR1 (Ren et al. 2009, Blood). To further investigate mechanisms of oncogenesis and progression, we undertook a global gene expression analysis of leukemic T-cells from the animal model compared with Thy1+DP+ (CD4+CD8+) cells isolated from normal Balb/c thymuses, as well as lukemic stem cells (LSK, GFP+Lin-Sca-1+c-kit+ cells) sorted from the leukemic mice versus hematopoietic stem cells (HSC, Lin-Sca-1+c-kit+ cells) sorted from normal BALB/c bone marrow cells. We found high expressions of Notch1 and its downstream target genes in T-cell lymphomas that arise in a murine model of ZMYM2-FGFR1 SCLL. Our functional studies demonstrate the importance of Notch signaling in the etiology of SCLL and suggest that targeting this pathway could provide a novel strategy for molecular therapies to treat SCLL patients.

2012-02-14 | GSE28823 | GEO

Genome-wide profiling of miRNA associated with BCR-FGFR1 fusion kinase driven stem cell leukemia and lymphoma II

Project description:The BBC1 and BBC2 cell lines were isolated from pre-B-cell lymphoma models of a murine BCR-FGFR1 driven SCLL. miRNA profiles for BBC2 cells, were established using miRNA arrays. First, BBC2 cells were compared with FACS sorted, normal, murine splenic CD19+ B cells isolated from BALB/c mice, where upregulated and downregulated miRNAs in BBC2 cells were identified. We next investigated which of these miRNAs were affected by loss of FGFR1 function. Previously we showed that the FGFR inhibitor BGJ398 suppresses suppressed phosphoactivation of chimeric FGFR1 kinases. When BBC2 cells were treated with 50nM BGJ398 for 24 hours, up- and down-regulated miRNAs by FGFR1 signaling were identified. By comparasion of the two subsets of differentially expressed miRNAs, we were able to define core candidate miRNAs which appear to be regulated by BCR-FGFR1 in SCLL.

2018-01-01 | GSE104895 | GEO

Genome-wide profiling of miRNA associated with BCR-FGFR1 fusion kinase driven stem cell leukemia and lymphoma I

2018-01-01 | GSE104894 | GEO

RET fusion genes, BCR-RET and FGFR1OP-RET, are associated with chronic myelomonocytic leukemia, display sensitivity to Sorafenib, an inhibitor of tyrosine-kinase activity and enhance monocytic differentiation

Project description:Myeloproliferative neoplasms are frequently associated with aberrant constitutive tyrosine kinase (TK) activity resulting from point mutations or chimaeric fusion genes, such as BCR ABL1 or JAK2 V617F. We report here for the first time in hematological malignancies, two novel fusion genes involving the TK RET, BCR-RET and FGFR1OP-RET, in chronic myelo monocytic leukemia (CMML) cases. The two RET fusion genes lead to the aberrant activation of RET, are able to transform hematopoietic cells and skew the hematopoietic differentiation program towards the monocytic/macrophage lineage. We also report that the BCR-RET fusion protein is insensitive to Imatinib but sensitive to Sorafenib in vivo. CMML is an hematopoietic malignancy associated with the frequent activation of the RAS pathway. The RET fusion genes seems to constitutively mimic the same signaling pathway than RAS mutations. Overall, the RET fusion genes behaviors in the monocytic lineage underlie the role of the normal RET TK activity during the physiological monocytic differentiation. We analysed BAF/3 cells infected by BCR-RET, FGFR1OP-RET or BCR-ABL1P210 fusion genes retroviruses and sorted out using EGFP fluorescence, with Affymetrix GeneChip MouseGene 1.0 ST platform.

2012-01-06 | E-GEOD-34900 | biostudies-arrayexpress

Genome-wide profiling of miRNA associated with BCR-FGFR1 fusion kinase driven stem cell leukemia and lymphoma I

Project description:Genome-wide profiling of miRNA associated with BCR-FGFR1 fusion kinase driven stem cell leukemia and lymphoma I

| PRJNA414102 | ENA

Genome-wide profiling of miRNA associated with BCR-FGFR1 fusion kinase driven stem cell leukemia and lymphoma II

Project description:Genome-wide profiling of miRNA associated with BCR-FGFR1 fusion kinase driven stem cell leukemia and lymphoma II

| PRJNA414101 | ENA

Identification of transcriptional network regulated by FGFR1 fusion kinase in stem cell leukemia and lymphoma (SCLL)

Project description:Purpose: Oncogenic transformation of hematopoietic stem cells by chimeric fusion kinases causing constitutive activation of FGFR1 leads to a stem cell leukemia/lymphoma (SCLL) syndrome, accompanied by widespread dysregulation of gene activity. The goals of this study are to use NGS-derived transcriptome profiling (RNA-seq) to identify genes regulated by FGFR1 fusion kinase in SCLL. Methods: Three different cell models for SCLL, respectively BBC2 (B cell lymphoblastic leukemia/lymphoma), ZNF112 (B cell lymphoblastic leukemia/lymphoma) and BCRF8C (myloid leukemia) were treated with selective FGFR1 kinase inhibitor,then the total RNA from treatment and viechel control were isolated for RNA-Seq analysis. Results: A global gene experssion change is generated, and provides fundamental information for demostration of molecular mechanisms in FGFR1 driven leukemogenesis.

2019-02-12 | GSE110457 | GEO

Molecular reprogramming of granulocyte/macrophage progenitor (GMP) clusters upon induction of BCR/ABL oncogene

Project description:Single cell RNA Seq and bioinformatic analysis are used to study what processes are important for the molecular reprogramming of GMPs once mice develop chronic myelogenous leukemia-like (CML-like) myeloproliferative neoplasm (MPN) upon induction of BCR/ABL oncogene.

2017-03-31 | GSE90797 | GEO

2012-01-06 | GSE34900 | GEO

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