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

Abstract:

: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.

journal_name

Blood

journal_title

Blood

authors

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

doi

10.1182/blood-2010-02-267344

subject

Has Abstract

pub_date

2011-04-28 00:00:00

pages

4409-19

issue

17

eissn

0006-4971

issn

1528-0020

pii

blood-2010-02-267344

journal_volume

117

pub_type

杂志文章

相关文献

BLOOD文献大全
  • CD5 and immunoglobulin V gene expression in B-cell lymphomas and chronic lymphocytic leukemia.

    abstract::We studied the expression of CD5 and immunoglobulin variable gene families in a panel of monoclonal Epstein-Barr virus (EBV) transformed lines, chronic lymphocytic leukemias (CLLs) and CD5+ and CD5- B-cell lymphomas. The CD5 gene expression was in all cases identical to that of T-cell malignancies. The utilization of ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Mayer R,Logtenberg T,Strauchen J,Dimitriu-Bona A,Mayer L,Mechanic S,Chiorazzi N,Borche L,Dighiero G,Mannheimer-Lory A

    更新日期:1990-04-01 00:00:00

  • G-CSF receptor activation of the Src kinase Lyn is mediated by Gab2 recruitment of the Shp2 phosphatase.

    abstract::Src activation involves the coordinated regulation of positive and negative tyrosine phosphorylation sites. The mechanism whereby receptor tyrosine kinases, cytokine receptors, and integrins activate Src is not known. Here, we demonstrate that granulocyte colony-stimulating factor (G-CSF) activates Lyn, the predominan...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-12-261636

    authors: Futami M,Zhu QS,Whichard ZL,Xia L,Ke Y,Neel BG,Feng GS,Corey SJ

    更新日期:2011-07-28 00:00:00

  • Frontline brentuximab vedotin in combination with dacarbazine or bendamustine in patients aged ≥60 years with HL.

    abstract::Patients aged ≥60 years with treatment-naive Hodgkin lymphoma (HL) have few treatment options and inferior survival due to treatment-related toxicities and comorbidities. This phase 2, nonrandomized, open-label study evaluated brentuximab vedotin (BV) monotherapy (results previously reported), BV plus dacarbazine (DTI...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2017-06-787200

    authors: Friedberg JW,Forero-Torres A,Bordoni RE,Cline VJM,Patel Donnelly D,Flynn PJ,Olsen G,Chen R,Fong A,Wang Y,Yasenchak CA

    更新日期:2017-12-28 00:00:00

  • Functional leukemia-associated antigen-specific memory CD8+ T cells exist in healthy individuals and in patients with chronic myelogenous leukemia before and after stem cell transplantation.

    abstract::Antigens implicated in the graft-versus-leukemia (GVL) effect in chronic myeloid leukemia (CML) include WT1, PR1, and BCR-ABL. To detect very low frequencies of these antigen-specific CD8+ T cells, we used quantitative polymerase chain reaction (qPCR) to measure interferon-gamma (IFN-gamma) mRNA production by peptide-...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-01-0150

    authors: Rezvani K,Grube M,Brenchley JM,Sconocchia G,Fujiwara H,Price DA,Gostick E,Yamada K,Melenhorst J,Childs R,Hensel N,Douek DC,Barrett AJ

    更新日期:2003-10-15 00:00:00

  • Treatment of hairy cell leukemia with recombinant alpha interferon: II. In vivo down-regulation of alpha interferon receptors on tumor cells.

    abstract::Interferons (IFNs) initiate their effects by interacting with specific high-affinity cell surface receptors, but little is known about the physiology of IFN receptor interaction in vivo. Treatment of patients suffering from hairy cell leukemia (HCL) with human recombinant alpha IFN results in significant tumor regress...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Billard C,Sigaux F,Castaigne S,Valensi F,Flandrin G,Degos L,Falcoff E,Aguet M

    更新日期:1986-03-01 00:00:00

  • Mode of action of iron (III) chelators as antimalarials: I. Membrane permeation properties and cytotoxic activity.

    abstract::We have designed two subfamilies of lipophilic iron (III) chelators previously termed reversed siderophores (RSFs). The agents display physicochemical properties that favor extraction of iron beyond membrane barriers of Plasmodium falciparum-infected red blood cells. We studied the in vitro antimalarial potency of RSF...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Lytton SD,Mester B,Dayan I,Glickstein H,Libman J,Shanzer A,Cabantchik ZI

    更新日期:1993-01-01 00:00:00

  • Rapid detection of intracellular SH2D1A protein in cytotoxic lymphocytes from patients with X-linked lymphoproliferative disease and their family members.

    abstract::Mutations in the SH2D1A gene have been described in most patients with the clinical syndrome of X-linked lymphoproliferative disease (XLP). The diagnosis of XLP is still difficult given its clinical heterogeneity and the lack of a readily available rapid diagnostic laboratory test, particularly in patients without a f...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2004-09-3651

    authors: Tabata Y,Villanueva J,Lee SM,Zhang K,Kanegane H,Miyawaki T,Sumegi J,Filipovich AH

    更新日期:2005-04-15 00:00:00

  • Detection of a novel truncating Merkel cell polyomavirus large T antigen deletion in chronic lymphocytic leukemia cells.

    abstract::Merkel cell polyomavirus (MCPyV) is detected in approximately 80% of Merkel cell carcinomas (MCC). Yet, clonal integration and truncating mutations of the large T antigen (LTAg) of MCPyV are restricted to MCC. We tested the presence and mutations of MCPyV in highly purified leukemic cells of 70 chronic lymphocytic leu...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-02-269829

    authors: Pantulu ND,Pallasch CP,Kurz AK,Kassem A,Frenzel L,Sodenkamp S,Kvasnicka HM,Wendtner CM,Zur Hausen A

    更新日期:2010-12-09 00:00:00

  • A prospective study of the usefulness of the measurement of platelet-associated IgG for the diagnosis of idiopathic thrombocytopenic purpura.

    abstract::The measurement of platelet-associated IgG (PAIgG) is a potentially useful diagnostic test for idiopathic thrombocytopenia purpura (ITP). However, the restricted application of PAIgG measurements to thrombocytopenic populations primarily comprised of ITP patients will artificially enhance its diagnosis specificity. Fo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kelton JG,Powers PJ,Carter CJ

    更新日期:1982-10-01 00:00:00

  • Complex formation with pentraxin-2 regulates factor X plasma levels and macrophage interactions.

    abstract::Recently, we have identified scavenger receptor class A member I (SR-AI) as a receptor for coagulation factor X (FX), mediating the formation of an FX reservoir at the macrophage surface. Here, we demonstrate that the FX/SR-AI-complex comprises a third protein, pentraxin-2 (PTX2). The presence of PTX2 is essential to ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2016-06-724351

    authors: Muczynski V,Aymé G,Regnault V,Vasse M,Borgel D,Legendre P,Bazaa A,Harel A,Loubière C,Lenting PJ,Denis CV,Christophe OD

    更新日期:2017-04-27 00:00:00

  • Lung parenchyma-derived IL-6 promotes IL-17A-dependent acute lung injury after allogeneic stem cell transplantation.

    abstract::Idiopathic pneumonia syndrome (IPS) is a relatively common, frequently fatal clinical entity, characterized by noninfectious acute lung inflammation following allogeneic stem cell transplantation (SCT), the mechanisms of which are unclear. In this study, we demonstrate that immune suppression with cyclosporin after SC...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-07-590232

    authors: Varelias A,Gartlan KH,Kreijveld E,Olver SD,Lor M,Kuns RD,Lineburg KE,Teal BE,Raffelt NC,Cheong M,Alexander KA,Koyama M,Markey KA,Sturgeon E,Leach J,Reddy P,Kennedy GA,Yanik GA,Blazar BR,Tey SK,Clouston AD,MacDon

    更新日期:2015-04-09 00:00:00

  • Polyamine concentrations in bone marrow aspirates of children with leukemia and other malignancies.

    abstract::High-pressure liquid chromatography analysis of polyamines in bone narrow from leukemic and nonleukemic subjects demonstrated increased concentrations of putrescine, spermidine, and spermine associated with increased cellularity. The most striking abnormality was the marked elevation of putrescine. Bone marrow polyami...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Rennert O,Miale T,Shukla J,Lawson D,Frias J

    更新日期:1976-04-01 00:00:00

  • Incidence of inhibitor development in a group of young hemophilia A patients treated exclusively with lyophilized cryoprecipitate.

    abstract::The incidence of neutralizing isoantibody formation to infused factor VIII in a cohort of 67 hemophilia A patients, born between January 1, 1971 and April 30, 1990, who had been treated exclusively with lyophilized cryoprecipitate, was 6% (5.3 per 1,000 patient years of observation). The age-dependent cumulative risk ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Peerlinck K,Rosendaal FR,Vermylen J

    更新日期:1993-06-15 00:00:00

  • A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells.

    abstract::An unmet need in cell engineering is the availability of a single transgene encoded, functionally inert, human polypeptide that can serve multiple purposes, including ex vivo cell selection, in vivo cell tracking, and as a target for in vivo cell ablation. Here we describe a truncated human EGFR polypeptide (huEGFRt) ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-02-337360

    authors: Wang X,Chang WC,Wong CW,Colcher D,Sherman M,Ostberg JR,Forman SJ,Riddell SR,Jensen MC

    更新日期:2011-08-04 00:00:00

  • In vitro characterization of the human recombinant soluble granulocyte-macrophage colony-stimulating factor receptor.

    abstract::We have cloned, expressed, and partially purified a naturally occurring, truncated, soluble form of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor alpha subunit to investigate its biochemical and biologic properties. The soluble receptor species lacks the transmembrane and cytoplasmic dom...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Brown CB,Beaudry P,Laing TD,Shoemaker S,Kaushansky K

    更新日期:1995-03-15 00:00:00

  • The FLT3 ligand is a direct and potent stimulator of the growth of primitive and committed human CD34+ bone marrow progenitor cells in vitro.

    abstract::The present studies investigated the effects of the recently cloned flt3 ligand (FL) on the in vitro growth and differentiation of primitive and committed subsets of human CD34+ bone marrow (BM) progenitor cells. FL alone was a weak growth stimulator of CD34+ BM cells, but synergistically and directly enhanced colony ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Rusten LS,Lyman SD,Veiby OP,Jacobsen SE

    更新日期:1996-02-15 00:00:00

  • The sphingosine 1-phosphate receptor agonist FTY720 supports CXCR4-dependent migration and bone marrow homing of human CD34+ progenitor cells.

    abstract::The novel immunosuppressant FTY720 activates sphingosine 1-phosphate receptors (S1PRs) that affect responsiveness of lymphocytes to chemokines such as stromal cell-derived factor 1 (SDF-1), resulting in increased lymphocyte homing to secondary lymphoid organs. Since SDF-1 and its receptor CXCR4 are also involved in bo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-03-0875

    authors: Kimura T,Boehmler AM,Seitz G,Kuçi S,Wiesner T,Brinkmann V,Kanz L,Möhle R

    更新日期:2004-06-15 00:00:00

  • Excellent outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome: a PIDTC report.

    abstract::Wiskott-Aldrich syndrome (WAS) is an X-linked disease caused by mutations in the WAS gene, leading to thrombocytopenia, eczema, recurrent infections, autoimmune disease, and malignancy. Hematopoietic cell transplantation (HCT) is the primary curative approach, with the goal of correcting the underlying immunodeficienc...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2019002939

    authors: Burroughs LM,Petrovic A,Brazauskas R,Liu X,Griffith LM,Ochs HD,Bleesing JJ,Edwards S,Dvorak CC,Chaudhury S,Prockop SE,Quinones R,Goldman FD,Quigg TC,Chandrakasan S,Smith AR,Parikh S,Dávila Saldaña BJ,Thakar MS,Phela

    更新日期:2020-06-04 00:00:00

  • Formation and functioning of the factor IXa-VIII complex on the surface of endothelial cells.

    abstract::The formation and functioning of the factor X activating complex on the surface of cultured human venous endothelial cells (HVEC) were investigated. To the HVEC monolayer human factors IXa, VIII, X, CaCl2, and S-2222 were added, and a gradually increasing activation of factor X was observed. The maximum activity of 88...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Váradi K,Elödi S

    更新日期:1987-02-01 00:00:00

  • Differential regulation of human B-lymphocyte tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin (TNF-beta) production by protein phosphatase 1 and 2A inhibitor.

    abstract::Tumor necrosis factor (TNF) and lymphotoxin (LT; TNF-beta) are major cytokines produced by B lymphocytes. Stimulation by okadaic acid, a phosphatase 1 and 2A inhibitor, markedly increased TNF mRNA accumulation and cytokine production. On the other hand, the accumulation of LT mRNA was not affected by okadaic acid desp...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Xia HZ,Kannapell CC,Fu SM,Sung SS

    更新日期:1993-11-01 00:00:00

  • Delta-like1-induced Notch1 signaling regulates the human plasmacytoid dendritic cell versus T-cell lineage decision through control of GATA-3 and Spi-B.

    abstract::Human early thymic precursors have the potential to differentiate into multiple cell lineages, including T cells and plasmacytoid dendritic cells (pDCs). This decision is guided by the induction or silencing of lineage-specific transcription factors. The ETS family member Spi-B is a key regulator of pDC development, w...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-05-2090

    authors: Dontje W,Schotte R,Cupedo T,Nagasawa M,Scheeren F,Gimeno R,Spits H,Blom B

    更新日期:2006-03-15 00:00:00

  • Nilotinib is associated with a reduced incidence of BCR-ABL mutations vs imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase.

    abstract::In patients with chronic myeloid leukemia, BCR-ABL mutations contribute to resistance to tyrosine kinase inhibitor therapy. We examined the occurrence of treatment-emergent mutations and their impact on response in patients from the ENESTnd phase 3 trial. At the 3-year data cutoff, mutations were detected in approxima...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2012-04-423418

    authors: Hochhaus A,Saglio G,Larson RA,Kim DW,Etienne G,Rosti G,De Souza C,Kurokawa M,Kalaycio ME,Hoenekopp A,Fan X,Shou Y,Kantarjian HM,Hughes TP

    更新日期:2013-05-02 00:00:00

  • Stimulation of murine colony-forming cells with high proliferative potential by the combination of GM-CSF and CSF-1.

    abstract::Granulocyte-macrophage colony-stimulating factor (GM-CSF) has previously been shown to stimulate granulocyte, macrophage, and megakaryocyte lineages to act as an erythroid burst-promoting activity and to stimulate limited replication of spleen colony-forming cells. Here we demonstrate that murine GM-CSF alone or in co...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: McNiece IK,Robinson BE,Quesenberry PJ

    更新日期:1988-07-01 00:00:00

  • alpha-thalassemia resulting from a negative chromosomal position effect.

    abstract::To date, all of the chromosomal deletions that cause alpha-thalassemia remove the structural alpha genes and/or their regulatory element (HS -40). A unique deletion occurs in a single family that juxtaposes a region that normally lies approximately 18-kilobase downstream of the human alpha cluster, next to a structura...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Barbour VM,Tufarelli C,Sharpe JA,Smith ZE,Ayyub H,Heinlein CA,Sloane-Stanley J,Indrak K,Wood WG,Higgs DR

    更新日期:2000-08-01 00:00:00

  • Cytokine regulation of the human burst-forming unit-megakaryocyte.

    abstract::The human burst-forming unit-megakaryocyte (BFU-MK) is a primitive megakaryocytic progenitor cell. A marrow cell population enriched for BFU-MK (CD34+ DR-) was obtained by monoclonal antibody labeling and fluorescence-activated cell sorting. CD34+DR- cells were assayed in a serum-depleted, fibrin clot culture system. ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Briddell RA,Hoffman R

    更新日期:1990-08-01 00:00:00

  • Exogenous insulin-like growth factor 1 enhances thymopoiesis predominantly through thymic epithelial cell expansion.

    abstract::Insulin-like growth factor 1 (IGF-1) enhances thymopoiesis but given the broad distribution of IGF-1 receptors (IGF-1Rs), its mechanism of action has remained unclear. To identify points of thymic regulation by IGF-1, we examined its effects on T-cell precursors, thymocytes, and thymic epithelial cells (TECs) in norma...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-04-149435

    authors: Chu YW,Schmitz S,Choudhury B,Telford W,Kapoor V,Garfield S,Howe D,Gress RE

    更新日期:2008-10-01 00:00:00

  • Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification.

    abstract::Multisystem Langerhans cell histiocytosis (MS-LCH) is associated with high mortality when patients have risk organ involvement (RO(+)) or are younger than 2 years. In an international randomized trial, LCH-II, we intensified their treatment: arm A consisted of 6 weeks of daily prednisone and weekly vinblastine followe...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2007-08-106211

    authors: Gadner H,Grois N,Pötschger U,Minkov M,Aricò M,Braier J,Broadbent V,Donadieu J,Henter JI,McCarter R,Ladisch S,Histiocyte Society.

    更新日期:2008-03-01 00:00:00

  • Quantification of the locomotive behavior of polymorphonuclear leukocytes in clot preparations.

    abstract::Time-lapse videotape recordings of polymorphonuclear leukocytes (PMNs) from clot preparations were used to quantify the locomotive behavior of individual PMNs from normal subjects. Tracings derived from the videotapes allow one to quantify multiple parameters of the locomotive behavior of PMNs--direction, distance, ra...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Howard TH

    更新日期:1982-05-01 00:00:00

  • Prion protein expression in human leukocyte differentiation.

    abstract::The cellular isoform of the prion protein (PrPC) is a small glycoprotein attached to the outer leaflet of the plasma membrane by a glycosylphosphatidylinositol anchor. This molecule is involved in the pathogenesis of prion diseases in both humans and animals. We have characterized the expression patterns of PrPC durin...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Dodelet VC,Cashman NR

    更新日期:1998-03-01 00:00:00

  • Predictors of death from chronic graft-versus-host disease after bone marrow transplantation.

    abstract::Chronic graft-v-host disease (chronic GVHD) is a frequent cause of late morbidity and death after bone marrow transplantation (BMT). The actuarial survival after onset of chronic GVHD in 85 patients was 42% (95%Cl = 29%, 54%) at 10 years. Baseline characteristics present at the onset of chronic GVHD (before therapy) i...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Wingard JR,Piantadosi S,Vogelsang GB,Farmer ER,Jabs DA,Levin LS,Beschorner WE,Cahill RA,Miller DF,Harrison D

    更新日期:1989-09-01 00:00:00