Lenalidomide targets clonogenic side population in multiple myeloma: pathophysiologic and clinical implications.


:Recurrence of multiple myeloma (MM) after therapy suggests the presence of tumor-initiating subpopulations. In our study, we performed flow cytometry-based Hoechst 33342 staining to evaluate the existence of a MM population with stem-like features known as side population (SP) cells. SP cells exhibit substantial heterogeneity in MM cell lines and primary MM cells; express CD138 antigen in MM cell lines; display higher mRNA expression and functional activity of ABCG2 transporter; and have a higher proliferation index compared with non-SP cells. We observed evidence for clonogenic potential of SP cells, as well as the ability of SP cells to regenerate original population. Moreover, SP cells revealed higher tumorigenicity compared with non-SP cells. Importantly, lenalidomide decreased the percentage and clonogenicity of SP cells, and also induced phosphorylation changes in Akt, GSK-3α/β, MEK1, c-Jun, p53, and p70S6K in SP cells. Adherence to bone marrow stromal cells (BMSCs) increased the percentage, viability, and proliferation potential of SP cells. Lenalidomide and thalidomide abrogated this stimulatory effect of BMSCs and significantly decreased the percentage of SP cells. Our studies demonstrate a novel mechanism of action for lenalidomide, namely targeting SP fraction, providing the framework for new therapeutic strategies targeting subpopulations of MM cells including presumptive stem cells.






Jakubikova J,Adamia S,Kost-Alimova M,Klippel S,Cervi D,Daley JF,Cholujova D,Kong SY,Leiba M,Blotta S,Ooi M,Delmore J,Laubach J,Richardson PG,Sedlak J,Anderson KC,Mitsiades CS




Has Abstract


2011-04-28 00:00:00
















  • Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies.

    abstract::Seventy-one patients with hematologic malignancies received bone marrow from a histocompatible sibling (n = 48) or a partially matched relative (n = 23) that had been depleted of CD5+ T cells with either an anti-CD5 mooclonal antibody (MoAb) plus complement (anti-Leu1 + C) or an anti-CD5 MoAb conjugated to ricin A cha...


    pub_type: 杂志文章


    authors: Antin JH,Bierer BE,Smith BR,Ferrara J,Guinan EC,Sieff C,Golan DE,Macklis RM,Tarbell NJ,Lynch E

    更新日期:1991-10-15 00:00:00

  • Hyaluronate-CD44 interactions can induce murine B-cell activation.

    abstract::CD44 is a widely distributed cell surface glycoprotein whose principal ligand has been identified as hyaluronic acid (HA), a major component of the extracellular matrix (ECM). Recent studies have demonstrated that activation through CD44 leads to induction of effector function in T cells and macrophages. In the curren...


    pub_type: 杂志文章


    authors: Rafi A,Nagarkatti M,Nagarkatti PS

    更新日期:1997-04-15 00:00:00

  • The hydroxyurea-induced small GTP-binding protein SAR modulates gamma-globin gene expression in human erythroid cells.

    abstract::Hydroxyurea (HU), a drug effective in the treatment of sickle cell disease, is thought to indirectly promote fetal hemoglobin (Hb F) production by perturbing the maturation of erythroid precursors. The molecular mechanisms involved in HU-mediated regulation of gamma-globin expression are currently unclear. We identifi...


    pub_type: 杂志文章


    authors: Tang DC,Zhu J,Liu W,Chin K,Sun J,Chen L,Hanover JA,Rodgers GP

    更新日期:2005-11-01 00:00:00

  • A novel P-selectin glycoprotein ligand-1 monoclonal antibody recognizes an epitope within the tyrosine sulfate motif of human PSGL-1 and blocks recognition of both P- and L-selectin.

    abstract::Interactions between P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) mediate the earliest "rolling" of leukocytes on the lumenal surface of endothelial cells at sites of inflammation. Previously, PSGL-1 has been shown to be the primary mediator of interactions between neutrophils and P-selectin, but studies o...


    pub_type: 杂志文章


    authors: Snapp KR,Ding H,Atkins K,Warnke R,Luscinskas FW,Kansas GS

    更新日期:1998-01-01 00:00:00

  • Excellent T-cell reconstitution and survival depend on low ATG exposure after pediatric cord blood transplantation.

    abstract::Successful immune reconstitution (IR) is associated with improved outcomes following pediatric cord blood transplantation (CBT). Usage and timing of anti-thymocyte globulin (ATG), introduced to the conditioning to prevent graft-versus-host disease and graft failure, negatively influences T-cell IR. We studied the rela...


    pub_type: 临床试验,杂志文章


    authors: Admiraal R,Lindemans CA,van Kesteren C,Bierings MB,Versluijs AB,Nierkens S,Boelens JJ

    更新日期:2016-12-08 00:00:00

  • Granulocyte-macrophage colony-stimulating factor mRNA stabilization enhances transgenic expression in normal cells and tissues.

    abstract::To increase transgenic production of granulocyte-macrophage colony-stimulating factor (GM-CSF), we mutated the mRNA's 3'-untranslated region, AUUUA instability elements. Expression vectors containing human or murine GM-CSF cDNAs coding for wild-type (GM-AUUUA) or mutant versions with reiterated AUGUA repeats (GM-AUGUA...


    pub_type: 杂志文章


    authors: Rajagopalan LE,Burkholder JK,Turner J,Culp J,Yang NS,Malter JS

    更新日期:1995-10-01 00:00:00

  • Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis, and therapeutic opportunities.

    abstract::Over the past 2 decades considerable evidence has accumulated on the association between hepatitis C virus (HCV) and hepatitis B virus (HBV) and several hematologic malignancies, most notably B-cell non-Hodgkin lymphoma (NHL). In this review we summarize this evidence, address possible mechanisms whereby hepatitis vir...


    pub_type: 杂志文章,评审


    authors: Marcucci F,Mele A

    更新日期:2011-02-10 00:00:00

  • Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation: long-term results in a series of 421 patients.

    abstract::Previous studies have suggested that, in patients with AL amyloidosis treated with high-dose melphalan and autologous stem-cell transplantation (HDM/SCT), the greatest benefit is seen in those patients achieving a hematologic complete response (CR). We analyzed a series of 421 consecutive patients treated with HDM/SCT...


    pub_type: 杂志文章


    authors: Cibeira MT,Sanchorawala V,Seldin DC,Quillen K,Berk JL,Dember LM,Segal A,Ruberg F,Meier-Ewert H,Andrea NT,Sloan JM,Finn KT,Doros G,Blade J,Skinner M

    更新日期:2011-10-20 00:00:00

  • Homozygous beta-thalassemia without anemia.

    abstract::A 37-year-old man of Guyanese origin was found to have homozygous beta-thalassemia without anemia. There were no physical stigmata of thalassemia. The hematocrit value was 41 to 45.8, the mean corpuscular volume was 61 fL, and the mean corpuscular hemoglobin was 18.9 pg. The HbF was 45% with a G gamma:A gamma ratio of...


    pub_type: 杂志文章


    authors: Safaya S,Rieder RF,Dowling CE,Kazazian HH Jr,Adams JG 3rd

    更新日期:1989-01-01 00:00:00

  • Molecular analysis of the structure and expression of the RH locus in individuals with D--, Dc-, and DCw- gene complexes.

    abstract::Rh blood group antigens of the D, C/c, and E/e series are carried by at least three red cell membrane polypeptides encoded by two highly related genes, RHD and RHCE. Homozygous individuals carrying the D--, Dc-, and DCw- gene complexes are characterized by a total or partial lack of expression of the RHCE-encoded anti...


    pub_type: 杂志文章


    authors: Chérif-Zahar B,Raynal V,D'Ambrosio AM,Cartron JP,Colin Y

    更新日期:1994-12-15 00:00:00

  • Expression of tumor-associated antigens in acute myeloid leukemia: Implications for specific immunotherapeutic approaches.

    abstract::The expression of tumor-associated antigens (TAAs) might play a critical role in the control of minimal residual disease (MRD) in acute myeloid leukemia (AML), and therefore might be associated with clinical outcome in AML. In a DNA microarray analysis of 116 AML samples, we found a significant correlation between hig...


    pub_type: 临床试验,杂志文章


    authors: Greiner J,Schmitt M,Li L,Giannopoulos K,Bosch K,Schmitt A,Dohner K,Schlenk RF,Pollack JR,Dohner H,Bullinger L

    更新日期:2006-12-15 00:00:00

  • Chemotherapy-only treatment effects on long-term neurocognitive functioning in childhood ALL survivors: a review and meta-analysis.

    abstract::Therapy for childhood acute lymphoblastic leukemia (ALL) is associated with 5-year survival rates of ∼90% even after largely eliminating cranial radiation. This meta-analysis assesses the long-term neurocognitive functioning after chemotherapy-only regimens among survivors of childhood ALL. We conducted a systematic r...


    pub_type: 杂志文章,meta分析,评审


    authors: Iyer NS,Balsamo LM,Bracken MB,Kadan-Lottick NS

    更新日期:2015-07-16 00:00:00

  • Factor VIII gene inversions in severe hemophilia A: results of an international consortium study.

    abstract::Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) ...


    pub_type: 杂志文章,多中心研究


    authors: Antonarakis SE,Rossiter JP,Young M,Horst J,de Moerloose P,Sommer SS,Ketterling RP,Kazazian HH Jr,Négrier C,Vinciguerra C,Gitschier J,Goossens M,Girodon E,Ghanem N,Plassa F,Lavergne JM,Vidaud M,Costa JM,Laurian Y,Lin

    更新日期:1995-09-15 00:00:00

  • Inhibition of BCR-ABL expression with antisense oligodeoxynucleotides restores beta1 integrin-mediated adhesion and proliferation inhibition in chronic myelogenous leukemia hematopoietic progenitors.

    abstract::Chronic myelogenous leukemia (CML) is characterized by the continuous proliferation and abnormal circulation of malignant hematopoietic progenitors. This may be related to the unresponsiveness of CML progenitors to beta1 integrin adhesion receptor-mediated inhibition of progenitor proliferation by the marrow microenvi...


    pub_type: 杂志文章


    authors: Bhatia R,Verfaillie CM

    更新日期:1998-05-01 00:00:00

  • Human dendritic cell subsets in NOD/SCID mice engrafted with CD34+ hematopoietic progenitors.

    abstract::Distinct human dendritic cell (DC) subsets differentially control immunity. Thus, insights into their in vivo functions are important to understand the launching and modulation of immune responses. We show that nonobese diabetic/LtSz-scid/scid (NOD/SCID) mice engrafted with human CD34+ hematopoietic progenitors develo...


    pub_type: 杂志文章


    authors: Palucka AK,Gatlin J,Blanck JP,Melkus MW,Clayton S,Ueno H,Kraus ET,Cravens P,Bennett L,Padgett-Thomas A,Marches F,Islas-Ohlmayer M,Garcia JV,Banchereau J

    更新日期:2003-11-01 00:00:00

  • Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized, placebo-controlled trial of the Eastern Cooperative Oncology Group 3999.

    abstract::Zosuquidar, which modulates P-glycoprotein (P-gp) with minimal delay of anthracycline clearance, may reverse P-gp-mediated resistance in acute myeloid leukemia without increased toxicity. A total of 449 adults older than 60 years with acute myeloid leukemia or high-risk myelodysplastic syndrome enrolled in a randomize...


    pub_type: 杂志文章,随机对照试验


    authors: Cripe LD,Uno H,Paietta EM,Litzow MR,Ketterling RP,Bennett JM,Rowe JM,Lazarus HM,Luger S,Tallman MS

    更新日期:2010-11-18 00:00:00

  • Clinical differences between nasal and extranasal natural killer/T-cell lymphoma: a study of 136 cases from the International Peripheral T-Cell Lymphoma Project.

    abstract::Among 1153 new adult cases of peripheral/T-cell lymphoma from 1990-2002 at 22 centers in 13 countries, 136 cases (11.8%) of extranodal natural killer (NK)/T-cell lymphoma were identified (nasal 68%, extranasal 26%, aggressive/unclassifiable 6%). The disease frequency was higher in Asian than in Western countries and i...


    pub_type: 杂志文章


    authors: Au WY,Weisenburger DD,Intragumtornchai T,Nakamura S,Kim WS,Sng I,Vose J,Armitage JO,Liang R,International Peripheral T-Cell Lymphoma Project.

    更新日期:2009-04-23 00:00:00

  • E47, IRF-4, and PU.1 synergize to induce B-cell-specific activation of the class II transactivator promoter III (CIITA-PIII).

    abstract::In B cells, expression of CIITA and resulting major histocompatibility complex II (MHCII) is mediated exclusively by promoter III (CIITA-PIII) activation. Recent studies have established that CIITA-PIII also participates in the expression of CIITA in activated human T cells, dendritic cells, and monocytes. In this stu...


    pub_type: 杂志文章


    authors: van der Stoep N,Quinten E,Marcondes Rezende M,van den Elsen PJ

    更新日期:2004-11-01 00:00:00

  • Localization of thrombospondin in clots formed in situ.

    abstract::Thrombospondin is a principal glycoprotein secreted by thrombin-stimulated platelets and has known affinities for fibrinogen and fibrin. We studied the distribution of thrombospondin in clots formed in situ on Formvar-coated coverslips at 37 degrees C for intervals up to 17 hours. The distributions of three other majo...


    pub_type: 杂志文章


    authors: Murphy-Ullrich JE,Mosher DF

    更新日期:1985-11-01 00:00:00

  • Mechanisms accounting for the defective natural killer activity in patients with hairy cell leukemia.

    abstract::Natural killer (NK) cell activity is severely impaired in untreated patients with hairy cell leukemia (HCL). In an attempt to investigate whether this impairment is related to a defect at the target cell binding and/or at the post target cell binding level, we evaluated the peripheral blood mononuclear cells (PBMC) of...


    pub_type: 杂志文章


    authors: Trentin L,Zambello R,Agostini C,Ambrosetti A,Chisesi T,Raimondi R,Bulian P,Pizzolo G,Semenzato G

    更新日期:1990-04-01 00:00:00

  • Effective contribution of transplanted vascular progenitor cells derived from embryonic stem cells to adult neovascularization in proper differentiation stage.

    abstract::We demonstrated that Flk-1(+) cells derived from mouse embryonic stem (ES) cells can differentiate into both endothelial cells (ECs) and mural cells (MCs) to suffice as vascular progenitor cells (VPCs). In the present study, we investigated the importance of the stage of ES cell differentiation on effective participat...


    pub_type: 杂志文章


    authors: Yurugi-Kobayashi T,Itoh H,Yamashita J,Yamahara K,Hirai H,Kobayashi T,Ogawa M,Nishikawa S,Nishikawa S,Nakao K

    更新日期:2003-04-01 00:00:00

  • Cyclophosphamide metabolism is affected by azole antifungals.

    abstract::We performed a randomized trial to compare the safety and efficacy of itraconazole with fluconazole in preventing fungal infections in patients undergoing allogeneic stem cell transplantation (SCT). Itraconazole (intravenous 200 mg daily, or oral solution 2.5 mg/kg 3 times daily) and fluconazole (intravenous or oral, ...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Marr KA,Leisenring W,Crippa F,Slattery JT,Corey L,Boeckh M,McDonald GB

    更新日期:2004-02-15 00:00:00

  • Bryostatin 1, a unique biologic response modifier: anti-leukemic activity in vitro.

    abstract::Bryostatin 1, a macrocyclic lactone isolated from the marine bryozoan Bugula neritina, has demonstrated both antineoplastic activity against the murine P388 leukemia line in vivo and stimulatory activity against mouse and human hematopoietic progenitors. We studied the effects of bryostatin 1 on the growth of human le...


    pub_type: 杂志文章


    authors: Jones RJ,Sharkis SJ,Miller CB,Rowinsky EK,Burke PJ,May WS

    更新日期:1990-03-15 00:00:00

  • Creation of a genetic system for analysis of the phagocyte respiratory burst: high-level reconstitution of the NADPH oxidase in a nonhematopoietic system.

    abstract::The phagocyte nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase was functionally reconstituted in monkey kidney COS-7 cells by transfection of essential subunits, gp91(phox), p22(phox), p47(phox), and p67(phox). COS-7 cells express the essential small guanosine 5'-triphosphatase, Rac1. Transge...


    pub_type: 杂志文章


    authors: Price MO,McPhail LC,Lambeth JD,Han CH,Knaus UG,Dinauer MC

    更新日期:2002-04-15 00:00:00

  • Mortalin and DJ-1 coordinately regulate hematopoietic stem cell function through the control of oxidative stress.

    abstract::Hematopoietic stem cells (HSCs) maintain stemness through various mechanisms that protect against stressful conditions. Heat shock proteins (HSPs) preserve cell homeostasis during stress responses through protein quality control, suggesting that HSPs may safeguard HSCs against numerous traumas. Here, we show that mort...


    pub_type: 杂志文章


    authors: Tai-Nagara I,Matsuoka S,Ariga H,Suda T

    更新日期:2014-01-02 00:00:00

  • Thioredoxin prolongs survival of B-type chronic lymphocytic leukemia cells.

    abstract::Thioredoxin (Trx) is a ubiquitous protein disulfide oxidoreductase with antioxidant, cytokine, and chemotactic properties. Previously, we showed that Trx, in synergy with interleukin 1 (IL-1), IL-2, IL-4, tumor necrosis factor alpha (TNF-alpha), and CD40-ligation induced S-phase entry and mitosis in normal B cells and...


    pub_type: 杂志文章


    authors: Nilsson J,Söderberg O,Nilsson K,Rosén A

    更新日期:2000-02-15 00:00:00

  • Mast cells are crucial for early inflammation, migration of Langerhans cells, and CTL responses following topical application of TLR7 ligand in mice.

    abstract::Until recently, IgE-activated mast cells have been regarded merely as effector cells of adaptive immune responses, involved in allergic reactions and mucosal immunity to parasites. Herein, we report that murine dermal mast cells, activated by local administration of a cream containing the synthetic TLR7 ligand imiquim...


    pub_type: 杂志文章


    authors: Heib V,Becker M,Warger T,Rechtsteiner G,Tertilt C,Klein M,Bopp T,Taube C,Schild H,Schmitt E,Stassen M

    更新日期:2007-08-01 00:00:00

  • Protein kinase Cdelta mediates retinoic acid and phorbol myristate acetate-induced phospholipid scramblase 1 gene expression: its role in leukemic cell differentiation.

    abstract::Although phospholipid scramblase 1 (PLSCR1) was originally identified based on its capacity to promote transbilayer movement of membrane phospholipids, subsequent studies also provided evidence for its role in cell proliferation, maturation, and apoptosis. In this report, we investigate the potential role of PLSCR1 in...


    pub_type: 杂志文章


    authors: Zhao KW,Li X,Zhao Q,Huang Y,Li D,Peng ZG,Shen WZ,Zhao J,Zhou Q,Chen Z,Sims PJ,Wiedmer T,Chen GQ

    更新日期:2004-12-01 00:00:00

  • Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: a possible protective effect against disease progression.

    abstract::Exposure to HIV-1 does not necessarily result in infection and progression toward disease, thus suggesting that the control of viral infection may be achieved. Antibodies to CCR5 have been detected in HIV-exposed but uninfected subjects (ESNs); thus, these antibodies could be involved in HIV protection. To assess whet...


    pub_type: 杂志文章


    authors: Pastori C,Weiser B,Barassi C,Uberti-Foppa C,Ghezzi S,Longhi R,Calori G,Burger H,Kemal K,Poli G,Lazzarin A,Lopalco L

    更新日期:2006-06-15 00:00:00

  • Platelet-melanoma cell interaction is mediated by the glycoprotein IIb-IIIa complex.

    abstract::A human malignant melanoma cell line (M3Dau) was observed by electron microscopy to interact directly with human platelets and induced platelet aggregation. Fab fragments of a monoclonal antibody MoAb (LYP18), directed against the platelet glycoprotein (GP) IIb-IIIa complex, inhibited platelet-melanoma interactions an...


    pub_type: 杂志文章


    authors: Boukerche H,Berthier-Vergnes O,Tabone E,Doré JF,Leung LL,McGregor JL

    更新日期:1989-08-01 00:00:00