Establishment of the B cell precursor acute lymphoblastic leukemia cell line MUTZ-5 carrying a (12;13) translocation

Meyer, Corinna; MacLeod, Roderick A.F.; Quentmeier, Hilmar; Janssen, J. W. G.; Coignet, Lionel; Dyer, Martin J. S.; Drexler, Hans G.

doi:10.1038/sj.leu.2402212

Cited by 6 publications

(2 citation statements)

References 11 publications

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“…RPMI 8226, U266 (MM cell lines), and MRC5 (immortalized fibroblasts) were obtained from the American Type Culture Collection ([ATCC] Manassas, VA); K620, an IgG-plasma cell leukemia cell line, 22 and DoHH2 (transformed non-Hodgkin lymphoma [NHL]) 23 were a gift from Dr Elisabeth Nacheva (Royal Free Hospital, London, United Kingdom); KMSM-1 and -2 (2 unpublished cell lines established from plasma cell leukemia patients presenting an IgG-light chain expression) were a gift from Dr Masami Nagai (Kagawa University, Japan); MM1-S and -R (dexamethasone sensitive and resistant, respectively) were a gift from Dr Steve Rosen (Northwestern University, Chicago, IL); EBV-LIN (lymphoblastoid cell line/immortalized lymphocytes) was a gift from Dr Thomas Ellis (The Blood Center of South Eastern Wisconsin, Milwaukee, WI); and the MUTZ5 (acute lymphoblastic leukemia [ALL]) cell line 24 was a gift from Dr Hans Drexler (DSMZ, Braunschweig, Germany). NIH 3T3 fibroblasts transfected with full-length human JAG2 cDNA (by L.M.)…”

Section: Samples and Cell Linesmentioning

confidence: 99%

Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines

Houde

Song

et al. 2004

Blood

157

149

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The NOTCH ligand, JAG2, was found to be overexpressed in malignant plasma cells from multiple myeloma (MM) patients and cell lines but not in nonmalignant plasma cells from tonsils, bone marrow from healthy individuals, or patients with other malignancies. In addition, JAG2 overexpression was detected in 5 of 5 patients with monoclonal gammopathy of undetermined significance (MGUS), an early phase of myeloma disease progression. This overexpression appears to be a consequence of hypomethylation of the JAG2 promoter in malignant plasma cells. An in vitro coculture assay was used to demonstrate that JAG2 induced the secretion of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and insulinlike growth factor-1 (IGF-1) in stromal cells. Further, the induction of IL-6 secretion was blocked in vitro by interference with anti-Notch-1 monoclonal antibodies raised against the binding sequence of Notch-1 with JAG2. Taken together, these results indicate that JAG2 overexpression may be an early event in the pathogenesis of multiple myeloma involving

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Section: Samples and Cell Linesmentioning

confidence: 99%

Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines

Houde

Song

et al. 2004

Blood

157

149

View full text Add to dashboard Cite

show abstract

“…Deletion of the wild-type allele of ETV6 in REH cells supported the tumor suppressor status of this gene and indicated a potential mechanism of escaping IRX3-mediated activation. Cell line MUTZ-5 contains the uncharacterized chromosomal aberration t(12;13)(p12;q13-14) which may be etiologically related to the deletion of both alleles of ETV6 at 12p13 [ 38 ]. Accordingly, ETV6 deletion prevents activation by IRX3 in this cell line as well.…”

Section: Discussionmentioning

confidence: 99%

Normal and Aberrant TALE-Class Homeobox Gene Activities in Pro-B-Cells and B-Cell Precursor Acute Lymphoblastic Leukemia

Nagel

Meyer

2022

IJMS

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Homeobox genes encode transcription factors regulating basic developmental processes. They are arranged according to sequence similarities of their conserved homeobox in 11 classes, including TALE. Recently, we have reported the so-called TALE-code. This gene signature describes physiological expression patterns of all active TALE-class homeobox genes in the course of hematopoiesis. The TALE-code allows the evaluation of deregulated TALE homeobox genes in leukemia/lymphoma. Here, we extended the TALE-code to include the stages of pro-B-cells and pre-B-cells in early B-cell development. Detailed analysis of the complete lineage of B-cell differentiation revealed expression of TALE homeobox genes IRX1 and MEIS1 exclusively in pro-B-cells. Furthermore, we identified aberrant expression of IRX2, IRX3 and MEIS1 in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) which originates from early B-cell progenitors. The data showed correlated activities of deregulated TALE-class members with particular BCP-ALL subtype markers, namely IRX2 with TCF3/E2A-fusions, IRX3 with ETV6/TEL-fusions, and MEIS1 with KMT2A/MLL-fusions. These correlations were also detected in BCP-ALL cell lines which served as experimental models. We performed siRNA-mediated knockdown experiments and reporter gene assays to analyze regulatory connections. The results showed mutual activation of IRX1 and TCF3. In contrast, IRX2 directly repressed wild-type TCF3 while the fusion gene TCF3::PBX1 lost the binding site for IRX2 and remained unaltered. IRX3 mutually activated fusion gene ETV6::RUNX1 while activating itself by aberrantly expressed transcription factor KLF15. Finally, KMT2A activated MEIS1 which in turn supported the expression of IRX3. In summary, we revealed normal TALE homeobox gene expression in early B-cell development and identified aberrant activities of IRX2, IRX3 and MEIS1 in particular subtypes of BCP-ALL. Thus, these TALE homeobox genes may serve as novel diagnostic markers and therapeutic targets.

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Identification of new therapeutic targets inCRLF2-overexpressing B-ALL through discovery of TF-gene regulatory interactions

Badri

Carella

Lhoumaud

et al. 2019

Preprint

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CRLF2 overexpression in B-ALL patients with an IGH-CRLF2 translocation activates JAK-STAT, PI3K and ERK/MAPK signaling pathways. Although inhibitors of these pathways are available, investigating alternate targets could reduce treatment-associated toxicities.Comparing RNA-seq from IGH-CRLF2 and non-translocated patients we defined a translocation gene signature. Next, we assembled a B-ALL cancer-specific regulatory network using 529 B-ALL patient samples from the NCI TARGET database coupled with priors generated from ATAC-seq peak TF-motif analysis. The network was used to infer differential changes in TF activities predicted to control IGH-CRLF2 deregulated genes, thereby enabling identification of translocation-associated pathways and potential new therapeutic targets.

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Establishment of the B cell precursor acute lymphoblastic leukemia cell line MUTZ-5 carrying a (12;13) translocation

Cited by 6 publications

References 11 publications

Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines

Overexpression of the NOTCH ligand JAG2 in malignant plasma cells from multiple myeloma patients and cell lines

Normal and Aberrant TALE-Class Homeobox Gene Activities in Pro-B-Cells and B-Cell Precursor Acute Lymphoblastic Leukemia

Identification of new therapeutic targets inCRLF2-overexpressing B-ALL through discovery of TF-gene regulatory interactions

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