scholarly journals Incorporation and Effect of Arachidonic Acid on the Growth of Human Myeloma Cell Lines

1999 ◽  
Vol 8 (2) ◽  
pp. 115-118 ◽  
Author(s):  
V. Desplat ◽  
C. Dulery ◽  
V. Praloran ◽  
Y. Denizot
Keyword(s):  
Arachidonic Acid ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Base Hydrolysis ◽  
Membrane Phospholipids ◽  
Myeloma Cells ◽  
Lipoxygenase Products ◽  
Kinetics Of ◽  
Phospholipid Species ◽  
Human Myeloma Cell

The objectives of this work are to investigate the incorporation of arachidonic acid (AA) in the human myeloma cell lines OPM2, U266 and IM9, and to assess the effect of AA and lipoxygenase products of AA on their growth. The kinetics of acylation of [3H]AA indicates that myeloma cells incorporate AA into their membrane phospholipids and triglycerides. PLA2-treatment and base hydrolysis experiments confirm that [3H]AA is incorporated unmodified in U266, IM9 and OPM2 phospholipids, and is linked by an ester bond. Prelabeling-chase experiments indicate no trafficking of labeled AA among the various phospholipid species. Addition of AA and lipoxygenase products of AA (leukotriene B4and C4, lipoxin A4and B4, 12- and 15-hydroxyeicosatetraenoic acid) have no effect on U266, IM9 and OPM2 proliferation assessed by [3H]thymidine incorporation into DNA. In conclusion, while human myeloma cells readily incorporate AA in their membrane phospholipids and triglycerides, AA and lipoxygenase products are not important modulators of their proliferation.

scholarly journals Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6

Blood ◽  
1989 ◽  
Vol 73 (2) ◽  
pp. 517-526 ◽  
Author(s):  
B Klein ◽  
XG Zhang ◽  
M Jourdan ◽  
J Content ◽  
F Houssiau ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Lines ◽  
Interleukin 6 ◽  
Neutralizing Antibodies ◽  
Myeloma Cell ◽  
B Cell Differentiation ◽  
Myeloma Cells ◽  
Autocrine Regulation ◽  
Spontaneous Proliferation ◽  
Human Myeloma Cell

Abstract To explore the mechanisms involved in the pathogenesis of human multiple myeloma (MM), we investigated the potential role of interleukin-6 (IL-6), a B-cell differentiation factor in humans, and a growth factor for rat/mouse heterohybridomas and murine plasmacytomas. Using a heterohybridoma assay, we found that two well-documented human myeloma cell lines, RPMI 8226 and U266, did not secrete IL-6 and did not express RNA messengers for IL-6. Neutralizing antibodies to IL-6 did not inhibit their proliferation, and recombinant IL-6 did not stimulate it. Taken together, these data show that IL-6 is not the autocrine growth factor of these human myeloma cell lines. A high production of IL-6 was found in the bone marrows of patients with fulminating MM, compared with patients with inactive or slightly active MM, or to healthy donors. This IL-6 production was assigned to adherent cells of the bone-marrow environment but not to myeloma cells. A spontaneous proliferation of myeloma cells freshly isolated from patients was observed in short-term cultures. Recombinant IL-6 was able to amplify it two- to threefold. The spontaneous proliferation of the myeloma cells was inhibited by anti-IL-6 antibodies and reinduced by recombinant IL-6. After 2 to 3 weeks of culture, the myeloma-cell proliferation progressively declined and no IL-6-dependent myeloma cell lines could be obtained despite repeated additions of fresh IL-6 and costimulation with other cytokines such as tumor necrosis factor (TNF)beta, or IL-1 beta. These data demonstrated a paracrine but not autocrine regulation of the growth and differentiation of myeloma cells by IL-6.

Upregulation of MMP-2 & 9 by Co-Culture of Human Myeloma Cell Lines and Endothelial Cells May Be Responsible for Protection Against Cytotoxic Drugs.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5080-5080
Author(s):  
Shankaranarayana Paneesha ◽  
Raghu Adya ◽  
Hemali Khanji ◽  
Ed Leung ◽  
C. Vijayasekar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Mrna Expression ◽  
Cell Lines ◽  
Myeloma Cell ◽  
Myeloma Cells ◽  
Human Myeloma Cell

Abstract Multiple myeloma is a clonal lymphoproliferative disorder characterised by the proliferation of plasma cells in the bone marrow. Inspite of good initial response, it is associated with universal relapse. We hypothesise this is due to sanctuary provided to myeloma cells by the endothelium. Matrix metalloproteinases (MMPs) are shown play a role in cell growth, invasion, angiogenesis, metastasis and bone degradation. We show here the protection offered by endothelial cells to human myeloma cell lines in in-vitro co-culture with upregulation of MMP-2 & 9 and the role of GM6001 MMP inhibitor (Ilomastat) in overcoming this protection. Human myeloma cell lines (H929, RPMI 8226, U266 & JJN3) with or without endothelial cells (human umbilical vein endothelial cells and EaHy 926 cell line) in-vitro co-culture were treated with melphalan, dexamethasone, arsenic trioxide and Ilomastat. Cytotoxicity/proliferation were assessed by the alamarBlue™ assay (Serotec) and validated by Annexin V-FITC apoptosis detection Kit (Calbiochem) and BrDU proliferation assay (BD Pharmingen™). Gelatin Zymography was used to demonstrate activity of MMP-2 & 9 in the supernatant. MMP-2 and 9 mRNA expression was quantified by Real Time Quantitative PCR (ROCHE). Co-culture of human myeloma cell lines with endothelial cells lead to increase in the proliferation of myeloma cell lines and also protected them from the cytotoxicity of chemotherapeutic agents. MMP-2 & 9 activity was upregulated by the co-culture. MMP-2 mRNA expression in human myeloma cell lines increased following 4 hr co-culture. Treatments with Ilomastat lead to the suppression of proliferation in co-culture in a dose dependent manner, associated with a reduction of MMP-2 and 9 activity. Our study shows endothelial cells offer protection to human myeloma cell lines in the presence of cytotoxic agents. This may result in the sanctuary of myeloma cells in bone marrow leading to ultimate relapse of disease. Our study also demonstrates the upregulation of MMP-2 and 9 by co-culture and increased cytotoxicity achieved by the inhibition of MMPs. Further studies are needed to determine the exact role of MMPs in myeloma biology as MMP inhibition may be an interesting therapeutic target and help in averting relapse in multiple myeloma.

Single-Cell Transcriptomics Identifies Intra-Tumor Heterogeneity in Human Myeloma Cell Lines

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3385-3385 ◽  
Author(s):  
Amit Kumar Mitra ◽  
Holly Stessman ◽  
Michael A. Linden ◽  
Brian Van Ness
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Cell Lines ◽  
Tumor Heterogeneity ◽  
Myeloma Cell ◽  
Gene Model ◽  
Color Flow ◽  
Myeloma Cells ◽  
Genetic Signature ◽  
Human Myeloma Cell

Abstract Multiple myeloma (MM) is a plasma cell neoplasm with significant complexity and heterogeneity. Proteasome inhibitors (PI) including bortezomib (Velcade/Bz), carfilzomib (Kyprolis/Cz) and Ixazomib are effective chemotherapeutic agents in the treatment of MM, used alone or in combination with other anti-cancer agents. However, in spite of the recent improvements in treatment strategies, MM still remains a difficult disease to cure with median survival rate of around 7 years. In a recently published study, we have shown that the heterogeneity in response to proteasome inhibitor (PI)-based treatment in MM is governed by underlying molecular characteristics of the subclones within tumor population (Stessman et al. 2013). We confirmed the presence of residual resistant sub-population comprising up to 15% of the bulk Bz-sensitive cell population in drug-naïve MM tumors. We hypothesize that this pre-existing resistant sub-population may give rise to emerging resistance in course of treatment with PIs. In the current study, we used single cell transcriptomics analysis to identify tumor subclones within Human Myeloma Cell Lines (HMCLs) based on a 48-gene model of predictive genetic signature for baseline PI response. Automated single-cell capture and cDNA synthesis from cellular RNA were performed using Fluidigm’s C1TM Single-Cell Auto Prep System. The cDNA was then harvested and transferred to BioMark HD System for single-cell targeted high-throughput qPCR-based gene expression analysis of a 48 gene-panel using Fluidigm DELTAgene assays. Our 48-gene model combines our previously published 23 gene expression profiling (GEP) signature that could discriminate between sensitive and resistant responsiveness to Bz, and the Shaughnessy et al prognostic 17-gene GEP model along with control genes, including cell cycle genes, anti-apoptotic genes, proteasome subunit genes, house-keeping genes and internal negative controls. Based on the differential expression of these 48 genes used in the modeling, distinct subclonal populations were then identified using a combination of Fluidigm’s analysis software and the R Statistical analysis package. Further, a principal component analysis (PCA) score plot was generated as a two-dimensional grid to visualize the separate populations associated with resistant profiles. Finally, hierarchical clustering (HC) analysis was used to generate heat maps that group expression patterns associated with response. Our results demonstrated the presence of pre-existing subclones of cells within untreated myeloma cells with a characteristic genetic signature profile distinct from the pre-treatment overall (bulk) profile of myeloma cells. As an additional validation of subclonal architecture, we demonstrated the presence of subclones within HMCLs using multi-color flow cytometry. The results presented will help identify the presence and extent of intra-tumor heterogeneity in MM by single cell transcriptomics and may define residual pre-existing subclones resistant to PI therapies. Disclosures No relevant conflicts of interest to declare.

The PPARß Activation Mechanism Which Suppresses the Constitutive NF-kB Activity in Human Myeloma Cell Lines.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4739-4739
Author(s):  
Ken-ichiro Otsuyama ◽  
Jakia Amin ◽  
Saeid Abroun ◽  
Abul Islam ◽  
Karim Shamsasenjan ◽  
...  
Keyword(s):  
Cell Lines ◽  
Target Genes ◽  
Myeloma Cell ◽  
Activation Mechanism ◽  
Pcr Analysis ◽  
Myeloma Cells ◽  
Ppar Agonist ◽  
Stimulation Of ◽  
Human Myeloma Cell ◽  
Human Myeloma Cells

Abstract [Purpose] It is considered that human myeloma cells have the constitutively high NF-kB activity involved in survival and proliferation. PPAR (Peroxisome proliferator-activated receptor) ß is ubiquitously expressed in all cells and considered to be involved in the lipid metabolism and regulating the inflammatory response and cell proliferation. We already have found that adrenal cortex hormones (DHEA and DHEA-S etc), dexamethasone (Dex) and baicalein augmented the expression of reporter gene. However, it remain to be clarified the role of PPARß in human myeloma cells. We focus on the mechanism of PPARß suppressed NF-kB activity. [Method] To know NF-kB activity of human myeloma cells, we performed EMSA with NF-kB consensus oligo. To investigate NF-kB and PPARß after stimulation of PPAR agonist, we did EMSA with NF-kB and PPAR consensus oligo. To confirm whether it is repression according the NF-kB activity suppression accompanying PPARß activation to the interaction of PPARß and NF-kB, we conducted immunoprecipitation - western blot analysis. To check whether the expression of NF-kB target genes (cIAP1, Bcl-xL, etc) were suppressed after stimulation of PPAR agonist, we performed RT-PCR analysis. [Result and discussion] It was suggested that human myeloma cell lines have constitutive NF-kB activity, and its activity mainly regulated p50. NF-kB activity and its target genes were repressed by stimulation of PPAR agonist. From the above, it was suggested that the activated PPARß interacted NF-kB and then its activity was suppressed.

scholarly journals Expression of syndecan regulates human myeloma plasma cell adhesion to type I collagen

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 767-774 ◽  
Author(s):  
RC Ridley ◽  
H Xiao ◽  
H Hata ◽  
J Woodliff ◽  
J Epstein ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Adhesion ◽  
B Cells ◽  
Heparan Sulfate ◽  
Cell Lines ◽  
Type I Collagen ◽  
Myeloma Cell ◽  
Type I ◽  
Myeloma Cells ◽  
Human Myeloma Cell

The syndecans comprise a family of integral membrane proteoglycans that regulate cell behaviors by binding to extracellular matrix and binding growth factors. In mouse blood cells, syndecan expression is restricted to cells of the B-cell lineage where it is expressed by pre-B cells and plasma cells, but is absent from circulating B cells. In the present study, we examined the expression, structure, and function of syndecan on human myeloma cell lines and myeloma patient bone marrow cells. On myeloma cells, syndecan is a small (modal relative molecular mass [M(r)] = 120 Kd) heparan sulfate proteoglycan localized at the cell surface. Syndecan was detected by immunodot blotting on 7 of 10 human myeloma cell lines and by reverse transcriptase polymerase chain reaction on 10 of 14 patient samples. Cell binding assays show that myeloma cells expressing syndecan bind to type I collagen via heparan sulfate chains, while those cell lines not expressing syndecan do not bind to collagen. Furthermore, the cell lines expressing syndecan were negative for CD19 and CD45 staining, indicating that syndecan expression is restricted to tumors having a well-differentiated phenotype. We conclude that syndecan acts as a matrix receptor on human myeloma cells but is not expressed by all tumors, suggesting that syndecan may participate in regulating myeloma cell adhesion to the bone marrow stromal matrix.

scholarly journals Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6

Blood ◽  
1989 ◽  
Vol 73 (2) ◽  
pp. 517-526 ◽  
Author(s):  
B Klein ◽  
XG Zhang ◽  
M Jourdan ◽  
J Content ◽  
F Houssiau ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Lines ◽  
Interleukin 6 ◽  
Neutralizing Antibodies ◽  
Myeloma Cell ◽  
B Cell Differentiation ◽  
Myeloma Cells ◽  
Autocrine Regulation ◽  
Spontaneous Proliferation ◽  
Human Myeloma Cell

To explore the mechanisms involved in the pathogenesis of human multiple myeloma (MM), we investigated the potential role of interleukin-6 (IL-6), a B-cell differentiation factor in humans, and a growth factor for rat/mouse heterohybridomas and murine plasmacytomas. Using a heterohybridoma assay, we found that two well-documented human myeloma cell lines, RPMI 8226 and U266, did not secrete IL-6 and did not express RNA messengers for IL-6. Neutralizing antibodies to IL-6 did not inhibit their proliferation, and recombinant IL-6 did not stimulate it. Taken together, these data show that IL-6 is not the autocrine growth factor of these human myeloma cell lines. A high production of IL-6 was found in the bone marrows of patients with fulminating MM, compared with patients with inactive or slightly active MM, or to healthy donors. This IL-6 production was assigned to adherent cells of the bone-marrow environment but not to myeloma cells. A spontaneous proliferation of myeloma cells freshly isolated from patients was observed in short-term cultures. Recombinant IL-6 was able to amplify it two- to threefold. The spontaneous proliferation of the myeloma cells was inhibited by anti-IL-6 antibodies and reinduced by recombinant IL-6. After 2 to 3 weeks of culture, the myeloma-cell proliferation progressively declined and no IL-6-dependent myeloma cell lines could be obtained despite repeated additions of fresh IL-6 and costimulation with other cytokines such as tumor necrosis factor (TNF)beta, or IL-1 beta. These data demonstrated a paracrine but not autocrine regulation of the growth and differentiation of myeloma cells by IL-6.

scholarly journals Expression of syndecan regulates human myeloma plasma cell adhesion to type I collagen

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 767-774 ◽  
Author(s):  
RC Ridley ◽  
H Xiao ◽  
H Hata ◽  
J Woodliff ◽  
J Epstein ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Adhesion ◽  
B Cells ◽  
Heparan Sulfate ◽  
Cell Lines ◽  
Type I Collagen ◽  
Myeloma Cell ◽  
Type I ◽  
Myeloma Cells ◽  
Human Myeloma Cell

Abstract The syndecans comprise a family of integral membrane proteoglycans that regulate cell behaviors by binding to extracellular matrix and binding growth factors. In mouse blood cells, syndecan expression is restricted to cells of the B-cell lineage where it is expressed by pre-B cells and plasma cells, but is absent from circulating B cells. In the present study, we examined the expression, structure, and function of syndecan on human myeloma cell lines and myeloma patient bone marrow cells. On myeloma cells, syndecan is a small (modal relative molecular mass [M(r)] = 120 Kd) heparan sulfate proteoglycan localized at the cell surface. Syndecan was detected by immunodot blotting on 7 of 10 human myeloma cell lines and by reverse transcriptase polymerase chain reaction on 10 of 14 patient samples. Cell binding assays show that myeloma cells expressing syndecan bind to type I collagen via heparan sulfate chains, while those cell lines not expressing syndecan do not bind to collagen. Furthermore, the cell lines expressing syndecan were negative for CD19 and CD45 staining, indicating that syndecan expression is restricted to tumors having a well-differentiated phenotype. We conclude that syndecan acts as a matrix receptor on human myeloma cells but is not expressed by all tumors, suggesting that syndecan may participate in regulating myeloma cell adhesion to the bone marrow stromal matrix.

scholarly journals Phenotypic analysis of human myeloma cell lines

Blood ◽  
1989 ◽  
Vol 73 (2) ◽  
pp. 566-572
Author(s):  
C Duperray ◽  
B Klein ◽  
BG Durie ◽  
X Zhang ◽  
M Jourdan ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Myeloma Cell ◽  
Light Chains ◽  
Cell Phenotype ◽  
Phenotypic Analysis ◽  
Barr Virus ◽  
Human Myeloma Cell

Multiple myeloma (MM) is a B-cell malignancy characterized by the accumulation, primarily in bone marrow, of a clone of plasma cells. The nature of the stem cells feeding the tumoral compartment is still unknown. To investigate this special point, we have studied the phenotypes of nine well-known human myeloma cell lines (HMCLs) and compared them with those of normal lymphoblastoid cell lines (LCLs). Twenty-four clusters of differentiation involved in B lymphopoiesis were investigated using a panel of 65 monoclonal antibodies (MoAbs). For each cluster, the percentage of positive cells and the antigen density were determined, giving rise to a “quantitative phenotype”. We thus classified the HMCLs into two different groups: those with cytoplasmic mu chains (c mu+) and those without (c mu-). In the first (c mu+) group, comprising seven cell lines, the HMCLs had a phenotype of pre-B/B cells close to that of Burkitt's lymphoma cell lines. They expressed low densities of surface mu chains, without detectable cytoplasmic or surface light chains. Three of them were infected with the Epstein Barr virus (EBV). These c mu+ HMCLs bore most of the B-cell antigens except CD23. They expressed the CALLA antigen (CD10) and lacked the plasma-cell antigen PCA1. In contrast, LCLs expressed surface light chains, high densities of CD23, low densities of PCA1 antigen, and no CD10 antigen. The c mu- HMCLs had a plasma-cell phenotype, lacking most of the B-cell antigens and expressing high densities of PCA1 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals NCOR2 Mutations Are Associated with IMiD Resistance in Human Myeloma Cells

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-4
Author(s):  
Tomoaki Mori ◽  
Cristina Panaroni ◽  
Chukwuamaka Onyewadume ◽  
Noopur S. Raje
Keyword(s):  
Cell Lines ◽  
Protein Interaction ◽  
Enrichment Analysis ◽  
Myeloma Cell ◽  
Resistant Cell ◽  
Ppi Network ◽  
Myeloma Cells ◽  
Knock Out ◽  
Protein Protein Interaction ◽  
Bet Inhibitor

The immunomodulatory drug thalidomide, and its analogs, lenalidomide, and pomalidomide (IMiDs) have significantly changed the treatment paradigm of multiple myeloma (MM). Despite this progress, IMiD resistance develops in the majority of patients resulting in the development of refractory disease. Cereblon (CRBN), a direct target, has been implicated in IMiD resistance. However, alternate mechanisms of IMiD resistance independent of CRBN remain largely unknown. To understand and study the mechanisms responsible for the development of IMiD resistance, we created lenalidomide-resistant (Len-R) and pomalidomide-resistant (Pom-R) human myeloma MM.1s cell lines, by continuous culture in the presence of lenalidomide or pomalidomide for 3 months. Whole genome sequencing of these 2 resistant cell lines compared with parental MM.1s revealed 172 genes with exonic mutations in both Len-R and Pom-R myeloma cells. Furthermore, a protein-protein interaction (PPI) network was constructed based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The PPI network demonstrated 8 genes that scored a high degree of protein-protein interaction. Among these genes, we identified NCOR2, a corepressor that negatively regulates gene expression, as a downregulated gene in resistant cell lines. To study this further, we created NCOR2 knock out MM.1s cell lines using CRISPR/cas9 gene modification. Our data demonstrates that depletion of NCOR2 confers IMiD resistance independent to CRBN. Interestingly, Len-R, Pom-R and NCOR2 knock out MM.1s showed increased MYC protein expression, which is essential for myeloma cell survival and proliferation. A BET inhibitor, known to disrupt the binding of BRD4 to chromatin, inhibited the proliferation of Len-R and Pom-R and NCOR2 knock out MM.1s by completely suppressing MYC expression. These results indicate that NCOR2 down regulation in IMiD resistant cells induces MYC upregulation which may in part result in IMiD resistance. Our findings reveal a novel molecular mechanism associated with IMiD resistance, independent of CRBN and suggest that NCOR2-MYC pathway may be a new target for IMiD refractory patients. Disclosures Raje: Celgene: Consultancy.

scholarly journals An inhibitor of the EGF receptor family blocks myeloma cell growth factor activity of HB-EGF and potentiates dexamethasone or anti–IL-6 antibody-induced apoptosis

Blood ◽  
2004 ◽  
Vol 103 (5) ◽  
pp. 1829-1837 ◽  
Author(s):  
Karène Mahtouk ◽  
Michel Jourdan ◽  
John De Vos ◽  
Catherine Hertogh ◽  
Geneviève Fiol ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Growth Factor ◽  
Cell Growth ◽  
Cell Lines ◽  
Stromal Cells ◽  
Egf Receptor ◽  
Myeloma Cell ◽  
Factor Activity ◽  
Myeloma Cells ◽  
Induced Apoptosis

Abstract We previously found that some myeloma cell lines express the heparin-binding epidermal growth factor–like growth factor (HB-EGF) gene. As the proteoglycan syndecan-1 is an HB-EGF coreceptor as well as a hallmark of plasma cell differentiation and a marker of myeloma cells, we studied the role of HB-EGF on myeloma cell growth. The HB-EGF gene was expressed by bone marrow mononuclear cells in 8 of 8 patients with myeloma, particularly by monocytes and stromal cells, but not by purified primary myeloma cells. Six of 9 myeloma cell lines and 9 of 9 purified primary myeloma cells expressed ErbB1 or ErbB4 genes coding for HB-EGF receptor. In the presence of a low interleukin-6 (IL-6) concentration, HB-EGF stimulated the proliferation of the 6 ErbB1+ or ErbB4+ cell lines, through the phosphatidylinositol 3-kinase/AKT (PI-3K/AKT) pathway. A pan-ErbB inhibitor blocked the myeloma cell growth factor activity and the signaling induced by HB-EGF. This inhibitor induced apoptosis of patients'myeloma cells cultured with their tumor environment. It also increased patients' myeloma cell apoptosis induced by an anti–IL-6 antibody or dexamethasone. The ErbB inhibitor had no effect on the interaction between multiple myeloma cells and stromal cells. It was not toxic for nonmyeloma cells present in patients' bone marrow cultures or for the growth of hematopoietic progenitors. Altogether, these data identify ErbB receptors as putative therapeutic targets in multiple myeloma.

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