Growth Of Burkitt's Lymphoma Cells Research Articles

Circular ZDHHC11 supports Burkitt lymphoma growth independent of its miR-150 binding capacity.

We previously showed that MYC promoted Burkitt lymphoma (BL) growth by inhibiting the tumor suppressor miR-150, resulting in release of miR-150 targets MYB and ZDHHC11. The ZDHHC11 gene encodes three different transcripts including a mRNA (pcZDHHC11), a linear long non-coding RNA (lncZDHHC11) and a circular RNA (circZDHHC11). All transcripts contain the same region with 18 miR-150 binding sites. Here we studied the relevance of circZDHHC11, including this miR-150 binding site region, for growth of BL cells. CircZDHHC11 was mainly present in the cytoplasmic fraction in BL cells and its localization was not altered upon miR-150 overexpression. Knockdown of circZDHHC11 caused a strong inhibition of BL growth without affecting the expression levels of MYC, MYB, miR-150 and other genes. Overexpression of circZDHHC11 neither affected cell growth, nor rescued the phenotype induced by miR-150 overexpression. Genomic deletion of the miR-150 binding site region did not affect growth, nor did it change the effect of circZDHHC11 knockdown. This indicated that the miR-150 binding site region is dispensable for the growth promoting role of circZDHHC11. To conclude, our results show that circZDHHC11 is a crucial factor supporting BL cell growth independent of its ability to sponge miR-150.

Inhibition of the glutamate-cysteine ligase catalytic subunit with buthionine sulfoximine enhances the cytotoxic effect of doxorubicin and cyclophosphamide in Burkitt lymphoma cells

Burkitt lymphoma (BL) is a highly aggressive lymphoma that mainly affects children and young adults. Chemotherapy is effective in young BL patients but the outcome in adults is less satisfactory. Therefore, there is a need to enhance the cytotoxic effect of drugs used in BL treatment. Glutathione (GSH) is an important antioxidant involved in processes such as regulation of oxidative stress and drug detoxification. Elevated GSH levels have been observed in many cancers and were associated with chemoresistance. We previously identified GCLC, encoding an enzyme involved in GSH biosynthesis, as an essential gene in BL. We now confirm that knockout of GCLC decreases viability of BL cells and that the GCLC protein is overexpressed in BL tissues. Moreover, we demonstrate that buthionine sulfoximine (BSO), a known inhibitor of GCLC, decreases growth of BL cells but does not affect control B cells. Furthermore, we show for the first time that BSO enhances the cytotoxicity of compounds commonly used in BL treatment, doxorubicin, and cyclophosphamide. Given the fact that BSO itself was not toxic to control cells and well-tolerated in clinical trials, combination of chemotherapy with BSO may allow reduction of the doses of cytotoxic drugs required to obtain effective responses in BL patients.

The JAK2 inhibitor TG101209 exhibits anti-tumor and chemotherapeutic sensitizing effects on Burkitt lymphoma cells by inhibiting the JAK2/STAT3/c-MYB signaling axis

Constitutive activation of JAK2/STAT3 is a major oncogenic signaling event involved in the development of Burkitt lymphoma (BL). In the present study, we investigated the antilymphoma activity of TG101209, a specific JAK2 inhibitor, on EBV-positive and EBV-negative Burkitt lymphoma cell lines and primary BL cells. The results showed that TG101209 had a significant antilymphoma effect by inhibiting BL cell growth and inducing apoptosis along with cell differentiation toward mature B cells in vitro. We also found that TG101209 displayed significant synergistic action and a sensitizing effect on the anti-Burkitt lymphoma activity of doxorubicin. In vivo experiments indicated that TG101209 could suppress tumor growth and prolong the overall survival of BL cell-bearing mice. The mechanistic study indicated that TG101209, by suppressing the JAK2/STAT3/c-MYB signaling axis and crosstalk between the downstream signaling pathways, plays an antilymphoma role. These data suggested that TG101209 may be a promising agent or alternative choice for the treatment of BL.

The miR-26b-5p/KPNA2 Axis Is an Important Regulator of Burkitt Lymphoma Cell Growth.

The expression of several microRNAs (miRNAs) is known to be changed in Burkitt lymphoma (BL), compared to its normal counterparts. Although for some miRNAs, a role in BL was demonstrated, for most of them, their function is unclear. In this study, we aimed to identify miRNAs that control BL cell growth. Two BL cell lines were infected with lentiviral pools containing either 58 miRNA inhibitors or 44 miRNA overexpression constructs. Eighteen constructs showed significant changes in abundance over time, indicating that they affected BL growth. The screening results were validated by individual green fluorescent protein (GFP) growth competition assays for fifteen of the eighteen constructs. For functional follow-up studies, we focused on miR-26b-5p, whose overexpression inhibited BL cell growth. Argonaute 2 RNA immunoprecipitation (Ago2-IP) in two BL cell lines revealed 47 potential target genes of miR-26b-5p. Overlapping the list of putative targets with genes showing a growth repression phenotype in a genome-wide CRISPR/Cas9 knockout screen, revealed eight genes. The top-5 candidates included EZH2, COPS2, KPNA2, MRPL15, and NOL12. EZH2 is a known target of miR-26b-5p, with oncogenic properties in BL. The relevance of the latter four targets was confirmed using sgRNAs targeting these genes in individual GFP growth competition assays. Luciferase reporter assay confirmed binding of miR-26b-5p to the predicted target site for KPNA2, but not to the other genes. In summary, we identified 18 miRNAs that affected BL cell growth in a loss- or gain-of-function screening. A tumor suppressor role was confirmed for miR-26b-5p, and this effect could at least in part be attributed to KPNA2, a known regulator of OCT4, c-jun, and MYC.

Triptolide induces mitochondria-mediated apoptosis of Burkitt's lymphoma cell via deacetylation of GSK-3β by increased SIRT3 expression

Burkitt's lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma with rapid growth and dissemination propensity. Triptolide (TP), an active component extracted from Chinese herb Tripterygium wilfordii Hook f., has broad-spectrum anti-tumor activities. This study aimed to explore the in vitro and in vivo anti-cancer effects of TP on BL and the potential molecular mechanisms.In this study, the in vitro anti-tumor activity of TP was determined by CCK-8 and flow cytometry assays in Raji, NAMALWA and Daudi cells. The expression of SIRT3, phosphorylation and acetylation of glycogen synthase kinase-3β (GSK-3β) were analyzed by Western blot assay. Moreover, we examined the mitochondrial membrane potential by JC-1 method and measured apoptosis related protein using Western blot assay. BL xenograft model in NOD/SCID mice were established to evaluate the in vivo anti-cancer effect of TP.We discovered that TP inhibited BL cell growth and induced apoptosis in a dose-dependent manner. Loss of SIRT3 provides growth advances for BL cells. However, TP could up-regulate SIRT3 expression, which resulted in suppression of BL cells proliferation. GSK-3β was activated by SIRT3-mediated deacetylation, which subsequently induced mitochondrial translocation and accumulation of Bax and decrease of mitochondrial membrane potential. Anti-tumor studies in vivo showed that TP (0.36 mg/kg) inhibited the growth of BL xenografts in NOD/SCID mice with an inhibitory rate of 73.13%.Our data revealed that TP triggered mitochondrial apoptotic pathway in BL by increasing SIRT3 expression and activating SIRT3/GSK-3β/Bax pathway. This study indicated that TP is a potential anti-cancer Chinese herbal medicine against BL.

Dual inhibition of histone deacetylases and phosphoinositide 3-kinases: effects on Burkitt lymphoma cell growth and migration.

Burkitt lymphoma is a highly aggressive non-Hodgkin lymphoma that is characterized by MYC deregulation. Recently, the PI3K pathway has emerged as a cooperative prosurvival mechanism in Burkitt lymphoma. Despite the highly successful results of treatment that use high-dose chemotherapy regimens in pediatric Burkitt lymphoma patients, the survival rate of pediatric patients with progressive or recurrent disease is low. PI3Ks are also known to regulate cell migration, and abnormal cell migration may contribute to cancer progression and dissemination in Burkitt lymphoma. Little is known about Burkitt lymphoma cell migration, but the cooperation between MYC and PI3K in Burkitt lymphoma pathogenesis suggests that a drug combination could be used to target the different steps involved in Burkitt lymphoma cell dissemination and disease progression. The aim of this study was to investigate the effects of the histone deacetylase inhibitor suberoylanilide hydroxamic acid combined with the PI3K inhibitor LY294002 on Burkitt lymphoma cell growth and migration. The combination enhanced the cell growth inhibition and cell-cycle arrest induced by the PI3K inhibitor or histone deacetylase inhibitor individually. Moreover, histone deacetylase inhibitor/PI3K inhibitor cotreatment suppressed Burkitt lymphoma cell migration and decreased cell polarization, Akt and ERK1/2 phosphorylation, and leads to RhoB induction. In summary, the histone deacetylase inhibitor/PI3Ki combination inhibits cell proliferation and migration via alterations in PI3K signaling and histone deacetylase activity, which is involved in the acetylation of α-tubulin and the regulation of RhoB expression.

Intravenous Immunoglobulin G (IVIg) Suppresses HSP70-1 and Has Potential Therapeutic Effects Against Multiple Myeloma and Lymphoma

IntroductionIntravenous Immunoglobulin G (IVIg) has been in wide use for over 20 years and is approved for treatment of immune deficiencies, autoimmune disease and acute infections. The ability of IVIg to suppress inflammation would also suggest it has a role to play in suppressing the growth of malignant cells, particularly given the now accepted bidirectional relationship between inflammation and cancer. In several case reports, patients with malignancies such as Kaposi's sarcoma, thyroid cancer and peripheral nerve sheath tumors experienced remission of their malignancies after receiving IVIg for immune deficiency(Shoenfeld and Krause 2004). Furthermore, a clinical trial in patients with advanced melanoma also reported a therapeutic effect of the anti-inflammatory dose of IVIg of 2 g/Kg (Schachter, Katz et al. 2007). These reports suggest that the pooled IgG of over 10,000 healthy donors is an unrealized and potentially useful anti-cancer agent that may augment both current and new chemotherapy regimens. However, the mechanism of response may not be limited to effects on inflammation or immunity, and might include a direct effect on tumor cells. To address this, we investigated the effect of IVIg on cell lines of non-Hodgkin's lymphoma and multiple myeloma (MM). MethodsA panel of MM and other cell lines derived from Burkitt's lymphoma (BL) and mantle cell lymphoma (MCL) were treated with dialyzed IVIg (10 mg/ml), which is in the 1-2 g/Kg anti-inflammatory clinically achievable range. The effects were evaluated both alone or in combination with proteasome inhibitors, bortezomib (BZB) and carfilzomib (CFZ), or the HSP90 inhibitors 17AAG and AUY-922. The efficacy of these drugs have their clinical utility limited due to HSP70-1 induction hence, IVIg makes a good choice for combination therapy. ResultsTreatment with 10 mg/ml IVIg suppressed the growth of all cell lines at 3 days compared to the bovine serum albumin control. This effect was accompanied by a G1cell cycle arrest and suppression of pro-tumor cytokines including IL-6, IL-8, IL-10 and GM-CSF. The combination of IVIg with BZB or CFZ was synergistic, and IVIg also resensitized BZB-resistant MM cells to BZB. The combination of IVIg and the HSP90 inhibitors 17AAG or AUY-922 was highly synergistic at suppressing the cells growth. IVIg strongly suppressed the expression of HSP70-1 both alone and when induced by HSP90 inhibitors. Varying the sequence of administration revealed that pretreatment with IVIg for 24 hours was superior in growth suppression compared to simultaneous administration of IVIg with 17AAG or AUY922 or pretreatment with 17AAG or AUY-922. IVIg treatment also suppressed expression of mutant p53, for which HSP70-1 serves as a cochaperone. ConclusionsIVIg has a potent ability to suppress MM, MCL and BL cell growth, through a mechanism that may involve its suppression of HSP70-1 expression. We hypothesize that IVIg contains IgG against HSP70-1, which results in enhanced HSP70-1 turnover and blocks the heat shock response induced by proteasome and HSP90 inhibitors. This mechanism would raise the possibility that IVIg could enhance the efficacy of targeted inhibitors, and inhibit mechanisms used by malignancies to evade these agents. Given its long clinical experience and exceptional safety profile, IVIg could be rapidly incorporated into the treatment of hematological malignancies.ReferencesSchachter, J., U. Katz, et al. (2007). “Efficacy and safety of intravenous immunoglobulin in patients with metastatic melanoma.” Annals of the New York Academy of Sciences 1110: 305-314.Shoenfeld, Y. and I. Krause (2004). “i.v.IG for autoimmune, fibrosis, and malignant conditions: our experience with 200 patients.” Journal of clinical immunology 24(2): 107-114. Disclosures:Orlowski:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: The Takeda Oncology Company: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Resverlogix: Research Funding; Array Biopharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees.

Abstract A178: Epigallocatechin-3-gallate (EGCG) induces catalase-sensitive cell growth inhibition and AKT activation in Burkitt lymphoma cells.

Abstract Burkitt lymphoma is an aggressive non-Hodgkin's B cell lymphoma. It is typically treated with high intensity chemotherapy, which is associated with toxicities. Therefore, it is important to develop novel treatments for this disease. Studies have found that the green tea-derived compound, epigallocatechin-3-gallate (EGCG), may be effective in treating Burkitt lymphoma (Nakazato T. et. al., 2005 and Noda C. et. al., 2007). Another study showed that the phosphatidylinositide 3-kinase (PI3K)/AKT pathway is important for Burkitt lymphoma proliferation and survival (Schmizt R. et. al., 2012). Therefore the purpose of this current study is to investigate the connection between EGCG and the PI3K/AKT pathway in Burkitt lymphoma cells. To begin, it was evaluated whether EGCG would induce dose-dependent, catalase-sensitive growth inhibition of the sporadic Burkitt lymphoma cell lines, BL41-3, DG75, and Ramos. These cells were treated with EGCG at varying doses and also in the presence or absence of catalase followed by MTT analysis. EGCG induced a dose-dependent growth inhibition of all three Burkitt lymphoma cell lines and co-treatment with catalase prevented this effect. To determine the effects of EGCG on the PI3K/AKT pathway, BL41-3, DG75, and Ramos, were treated with 0, 20, 40, or 80 μM EGCG followed by Western analysis for phosphorylated AKT and total AKT. The results indicated that AKT phosphorylation is increased in all three cell lines following EGCG treatment. Lastly, it was investigated how inhibition of PI3K during EGCG treatment impacts the anti-proliferative effects seen with EGCG alone. To test this, BL41-3, DG75, and Ramos cells were treated with EGCG and an inhibitor of PI3K, LY294002, followed by MTT analysis. EGCG and LY294002 inhibited Burkitt lymphoma cell growth, although the degree of inhibition and the effect of combination treatment varied between the three cell lines. In conclusion, EGCG induced AKT phosphorylation along with a catalase-sensitive growth inhibition and the addition of a PI3K inhibitor had an additive growth inhibitory effect with EGCG. These results provide novel insight into the use of EGCG for the treatment of sporadic Burkitt lymphomas. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A178. Citation Format: Carl-Christian Van Doorn, Aaron M. Domina. Epigallocatechin-3-gallate (EGCG) induces catalase-sensitive cell growth inhibition and AKT activation in Burkitt lymphoma cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A178.

Japonicone A Suppresses Growth of Burkitt Lymphoma Cells through Its Effect on NF-κB

NF-κB, a transcriptional regulator of diverse genes involved in cell survival, proliferation, adhesion, and apoptosis, has been implicated in various malignancies. We discovered a potent natural NF-κB inhibitor, Japonicone A, from the traditional herb Inula japonica Thunb, evaluated its preclinical pharmacology and therapeutic activity, and investigated the underlying mechanisms of action for its antitumor activity. Various types of cancer and normal cells were exposed to Japonicone A for cytotoxicity screening, followed by determination of cell apoptosis and cell-cycle arrest. Western blotting, immunostaining, and gene reporter assay were used to analyze NF-κB activity. Two xenograft models were used for therapeutic efficacy evaluation. Japonicone A killed cancer cells but had low cytotoxicity to normal cells. Burkitt lymphoma cells were particularly sensitive. Japonicone A inhibited the growth and proliferation of Raji, BJAB, and NAMALWA lymphoma cells and resulted in G2-M phase arrest and apoptosis. Furthermore, exposure of cells to Japonicone A caused inactivation of the TNF-α-TAK1-IKK-NF-κB axis and inhibition of TNF-α-stimulated NF-κB activity and nuclear translocation, followed by downregulation of NF-κB target genes involved in cell apoptosis (Bcl-2, Bcl-xL, XIAP, TRAF2) and in the cell cycle and growth (cyclin D, c-Myc). Moreover, Japonicone A inhibited local growth and dissemination of cancer cells to multiple organs in vivo. Japonicone A exerts significant anticancer effects on Burkitt lymphoma cells in vitro and in vivo through targeting of the NF-κB signaling cascade. These results highlight the potential of Japonicone A as a chemotherapeutic agent and warrant its development as a therapy for lymphomas.

Abstract 4760: Inhibition of c-myc by the triterpenoid celastrol

Abstract c-Myc is a bHLH-ZIP transcription factor that is deregulated in a variety of human cancers. More specifically, c-Myc heterodimerizes with another bHLH-ZIP partner protein, Max, to bind to specific sequences (E-Boxes: CAC/TGTG) located near the transcriptional start sites of its numerous target genes. Because c-Myc's highly variable downstream effects are difficult to attack individually, directly inhibiting the association between c-Myc and Max association by interfering with their bHLH-ZIP-mediated heterodimerization has emerged as an attractive therapeutic strategy. Thus far, high throughput screens of chemical libraries have identified a number of small molecules that specifically inhibit the c-Myc-Max association. However, these synthetic compounds and their analogs are generally of low potency and therefore have limited clinical utility. Here we report identification of celastrol, a naturally occurring triterpenoid, as a potent c-Myc inhibitor. We sought to further assess celastrol's ability to inhibit c-Myc-Max interaction and cell growth, and determine its structure activity relationship. Surface plasmon resonance and electrophoretic mobility shift studies revealed that celastrol specifically binds to c-Myc and prevents both its interaction with Max, and subsequent DNA binding with a Kd in the low micromolar range. Co-immunoprecipitation studies confirmed that the dose-dependent disruption of c-Myc-Max heterodimers by celastrol could also be achieved in c-Myc-overexpressing human HL60 promyelocytic leukemia cells. Moreover, in vitro data demonstrated that celastrol significantly inhibited both HL60 and Burkitt's lymphoma cell growth with IC50s in the nanomolar range. However, modifications to the C-28 carboxylic acid group of celastrol eliminated c-Myc binding, suggesting that celastrol binds to c-Myc via this functional group. This structure activity relationship may provide a basis for the development of more pharmacologically suitable analogs. Together these results suggest that celastrol is among the most potent Myc-Max disruptors yet identified, and suggest a mechanism of action. Celastrol thus represents a promising new agent with which to target c-Myc and provides a new structural chemical platform for further pharmaceutical development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4760. doi:1538-7445.AM2012-4760

PNAEμ can significantly reduce Burkitt's lymphoma tumor burden in a SCID mice model: cells dissemination similar to the human disease

In human Burkitt's Lymphoma (BL) BRG cells, a t(8;14) translocation, placing c-myc near the Emu enhancer of the H chain locus, causes tumor expansion. Earlier, we showed that a peptide nucleic acid complementary to the Emu sequence (PNAEmu), specifically inhibited the expression of translocated c-myc and impaired the growth of BRG cells-induced subcutaneous tumors in mice suffering from severe combined immunodeficiency (SCID). In this study, the therapeutic potential of PNAEmu was evaluated in a systemic mouse model. BRG-BL cells transfected with the luciferase gene were inoculated intravenously into SCID mice resulting in a preferential expansion, similar to the one of human adult patients, in the abdominal cavity, central nervous system and bone marrow. The mice were chronically injected intraperitoneally either with PNAEmu or with control PNA. The treatment was stopped when the control animals developed severe neurological symptoms. As detected both by inspection at necropsy and imaging, overall tumor growth in PNAEmu-treated mice decreased by >80%. Histological and immunohistochemical studies showed, only in PNAEmu-treated mice, a substantially reduced BL cell growth at the major sites of invasion and vast areas of necrosis in the lymphomatous tissues, with concomitant c-myc expression downregulation. Altogether, the data support the therapeutic potential of PNAEmu in human adult BL.

Inhibition of Burkitt's lymphoma cells growth in SCID mice by a PNA specific for a regulatory sequence of the translocated c-myc

In Burkitt's lymphoma (BL) cells due to a t(8;14) chromosomal translocation c-myc is often placed in proximity to the Emu enhancer of the Ig locus and upregulated. We demonstrated that in BL cells a peptide nucleic acid (PNA), complementary to intronic Emu sequences (PNAEmuwt), specifically blocks the expression of the c-myc oncogene under the Emu enhancer control and inhibits BL cell growth in culture. Here, we investigated whether PNAEmuwt was also able to block tumor growth in SCID mice inoculated with human BL cell lines. After subcutaneous inoculum in mice BL cells reproducibly form tumors. Both pre-treatment of BL cells with PNAEmuwt before inoculum and chronic intravenous administration of PNAEmuwt to mice already inoculated with BL cells selectively caused increased latency of tumor appearance and decreased final tumor size. Tumors from PNAEmuwt-treated animals showed substantial areas of cell necrosis and of c-myc downregulation. Inhibition of tumor growth was specific and was not observed with PNAEmumut carrying sequence mutations and in BL cell lines where the translocated c-myc is not under the control of the Emu enhancer. These data confirm the potential therapeutic value of PNA targeted to regulatory non-coding regions.

Ｄｏｍｉｎａｎｔ‐ｎｅｇａｔｉｖｅ ＥＢＮＡ１によるＥＢウイルス腫ようの抑制

Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1), a latent viral protein consistently expressed in infected proliferating cells, is essentially required in trans to maintain EBV episomes in cells. Thus EBNA1 will be an appropriate target for specific molecular therapy against EBV-associated cancers. We constructed a mutant (mt) EBNA1 lacking the N-terminal-half, relative to wild-type (wt) EBNA1, and demonstrated that it exerted dominant-negative effects on maintenance of the viral episome from cells regardless of viral latency or tissue origin thereby leading to significant suppression of naturally EBV-harboring Burkitt's lymphoma cell growth in vitro and in vivo. Our mutant can act as dominant-negative (dn) EBNA1 and will afford an additional therapeutic strategy specifically targeting EBV-associated malignancies. The similar approach can be applicable to exploit novel remedial protocols against uncontrollable diseases caused by other persistently-infected viruses. In addition, dnEBNA1 may also provide a useful analytical tool for the possible oncogenic function(s) of wtEBNA1.

Retinoic Acid Induces Changes in c- fgr Proto-Oncogene mRNA Levels in Burkitt's Lymphoma Cells

The c- fgr proto-oncogene is expressed in Burkitt's lymphoma (BL) cells and cell lines derived from them. When Epstein-Barr virus (EBV)-negative BL cell lines that contain low levels of c- fgr mRNA are infected with EBV, transcription of the c- fgr gene is further induced. In this paper we show that treatment of EBV-negative and EBV-positive BL cell lines with all- trans retinoic acid also stimulates an increase in c- fgr mRNA levels, varying between 2- and 13-fold depending on the cell line. An increase is detectable 12 to 48 h after treatment, depending on the cell line, suggesting that the c- fgr gene is not regulated directly by retinoic acid but responds to other retinoic acid-induced changes in the cell. We also show that treatment of BL cell lines with all- trans retinoic acid either results in a dose-dependent decrease in growth rate, or has no effect on growth, depending on the cell line. It has previously been suggested that the c- fgr gene product might have a role in regulating the growth of BL cells, since treatment of the EBV-positive BL cell line Daudi with α-interferon results in a decrease in c- fgr mRNA levels followed by a decrease in growth rate. Our data indicate that there is no general correlation between c- fgr mRNA levels and growth rate in BL cells and so argue against a role for the c- fgr gene product in growth regulation in these cells.

Antisense oligodeoxynucleotide: inhibits Burkitt lymphoma cell growth

Antisense oligodeoxynucleotide: inhibits Burkitt lymphoma cell growth