Abstract:
:Mantle cell lymphoma (MCL) affects approximately 4500 patients/year in the US and demonstrates a male to female ratio of approximately 4:1. While the pathobiology underlying this ratio is unknown, the hematopoietic system is characterized by sex-related differences in androgen receptor (AR) expression, leading us to hypothesize that the male-biased incidence of MCL may reflect sex-related differences in AR signaling during MCL lymphomagenesis. To explore the AR axis in MCL, we evaluated AR expression in MCL cell lines and human tumors, and tested the impact of androgen pathway inhibition on MCL proliferation. AR transcript levels ranged up to ~26 fold higher in MCL lines vs non-MCL NHL lines (p = 0.006) and were correlated with expression of the canonical AR-regulated gene, prostate-specific antigen (PSA; r = 0.715, p = 0.001), consistent with functional AR activity. Patient-derived MCL samples demonstrated a range of AR expression. Treatment of four different MCL lines with the potent AR antagonist enzalutamide demonstrated suppression of proliferation across both male and female-derived cell lines. These data suggest androgen-axis blockade may represent a novel therapeutic modality in MCL. This novel treatment approach is currently under investigation in a phase II clinical trial of AR inhibition in patients with relapsed/refractory MCL.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Mostaghel EA,Martin PS,Mongovin S,Frayo S,Zhang A,Edlefsen KL,Press OW,Gopal AKdoi
10.1016/j.exphem.2017.01.001subject
Has Abstractpub_date
2017-05-01 00:00:00pages
34-38.e2eissn
0301-472Xissn
1873-2399pii
S0301-472X(17)30011-5journal_volume
49pub_type
杂志文章abstract::Lymphatic leukemia L1210-bearing semisyngeneic Balb/c x DBA/2Wf F1 (CD2F1) mice were subjected to chemoradiotherapy (2 x 100 mg/kg of cyclophosphamide i.p. and 1000 cGy of total body irradiation) and reconstitution with 10(7) syngeneic bone marrow cells i.v. The bone marrow obtained from leukemic mice was previously e...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::Decades-old findings supporting origin of F cells in adult life from adult-type progenitors and the in vitro and in vivo enhancement of fetal globin under stress conditions have been juxtaposed against recent mechanistic underpinnings. An updated molecular interrogation did not debunk prior conclusions on the origin o...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2020.09.195
更新日期:2020-12-01 00:00:00
abstract:OBJECTIVE:Approximately 60% of all anaplastic large-cell lymphomas (ALCL) contain a specific t(2;5)(p23;q35) chromosomal translocation leading to overexpression of NPM-ALK. As the chimeric tyrosine kinase is involved in tumorigenesis and pathogenesis of ALCL, we were interested to inhibit NPM-ALK expression using an ex...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)01084-6
更新日期:2003-03-01 00:00:00
abstract::The current knowledge concerning the blood supply to hematopoietic bone marrow during increased marrow metabolism is scanty. We have previously shown that an accelerated erythropoiesis in the awake rat is accompanied by a rapid increase in perfusion of the tibial marrow and its bony encasement. We have now measured bl...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::Fabry disease is a lysosomal storage disorder that is due to a deficiency in alpha-galactosidase A (alpha-gal A). Previously we have shown that a recombinant retrovirus synthesized for the transfer of the human alpha-gal A coding sequence was able to engineer enzymatic correction of the hydrolase deficiency in fibrobl...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00050-8
更新日期:1999-07-01 00:00:00
abstract::It has been demonstrated that genomic alterations of cells in the hematopoietic microenvironment could induce myelodysplastic syndromes (MDS) with ineffective hematopoiesis and dysmorphic hematopoietic cells, and subsequent transformation to acute myeloid leukemia. This investigation is the first attempt to correlate ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2012.10.009
更新日期:2013-02-01 00:00:00
abstract::Antisera from rabbits immunized with murine macrophage colony-stimulating factor (CSF-1) were evaluated for cross-reactivity with human urine CSF-1. One cross-reactive antiserum was used to purify CSF from human urine. The IgG fractions from normal rabbit serum and the anti-CSF serum were bound to cyanogen bromide-act...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract:OBJECTIVE:Mobilized peripheral blood (PB) progenitors are increasingly used in autologous and allogeneic transplantation. However, the short- and long-term engraftment potential of mobilized PB or bone marrow (BM) has not been directly compared. Although several studies showed that BM-derived Lin(-)CD34(-) cells contai...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00506-3
更新日期:2000-09-01 00:00:00
abstract::Benign constitutional neutropenia (BCN) is an asymptomatic condition characterized by mild chronic neutropenia in patients with no history of recurrent infections. Most patients are referred for further testing, increasing health care costs. We present an alternative form of assessment of individuals with BCN based on...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2018.10.007
更新日期:2019-01-01 00:00:00
abstract:OBJECTIVE:Donor T cells expressing lymph node homing receptors are the foremost initiators of acute graft-vs-host disease (aGVHD), and a high proportion of CD4(+)CCR7(+) T cells in human leukocyte antigen-matched allografts has been shown to confer a high risk of aGVHD without interfering in other outcomes. METHODS:Na...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2007.03.006
更新日期:2007-06-01 00:00:00
abstract::Disruption of ribosomal proteins is associated with hematopoietic phenotypes in cell culture and animal models. Mutations in ribosomal proteins are seen in patients with Diamond Blackfan anemia, a rare congenital disease characterized by red cell aplasia and distinctive craniofacial anomalies. A zebrafish screen uncov...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2011.11.007
更新日期:2012-03-01 00:00:00
abstract::Malignant osteopetrosis is a disorder characterized by a deficiency in osteoclast number or function. In one animal model of osteopetrosis, the op/op mouse, macrophage colony-stimulating factor (M-CSF) is absent, and the administration of M-CSF corrects the defects. We evaluated the serum of 13 patients with malignant...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Activation of the N-ras gene via coding region mutations has been previously documented in 25% of patients with acute myeloid leukemia (AML). Since overexpression of normal N-ras is also transforming in vitro, the N-ras promoter of AML patients was analyzed for the presence of promoter mutations that may affect expres...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract:OBJECTIVE:Several transcription factors determine the cell fate decision between granulocytes and monocytes, but the upstream signal transduction pathways that govern myelopoiesis are largely unknown. Based on our observation of aberrant myeloid cell representation in hematopoietic tissues of 12/15-lipoxygenase (12/15-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.07.004
更新日期:2010-11-01 00:00:00
abstract:OBJECTIVE:New nonmyeloablative strategies to improve acceptance of mismatched bone marrow (BM) may compensate for the inadequate supply of compatible grafts. Recently we proposed to facilitate engraftment of mismatched BM by selective depletion of activated donor-reactive host cells with cyclophosphamide (CY). Here we ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2004.07.017
更新日期:2004-11-01 00:00:00
abstract::An improved negative immunomagnetic selection strategy has been devised for the enrichment of primitive hemopoietic cells using the high proliferative potential colony-forming cell (HPP-CFC) assay as an index of stem cell purification. Immunomagnetic selection was carried out using goat anti-rat conjugated M-450 Dynab...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::Hematopoietic stem/progenitor cells (HSPCs) play important roles in fighting systemic infection as they supply immune cells in a demand-adapted manner. Various mechanisms govern HSPC responses to infection, including cytokine signaling, niche function, and direct sensing of pathogen-derived molecules by HSPCs themselv...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2015.11.008
更新日期:2016-02-01 00:00:00
abstract::C3H/Km flora-defined mice were used to investigate the effect of exposure to pulsing electromagnetic field (PEMF) after total body x-ray irradiation. Prolonged exposure to PEMF had no effect on normal nonirradiated mice. When mice irradiated with different doses of x-ray (8.5 Gy, 6.8 Gy, and 6.3 Gy) were exposed to PE...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-02-01 00:00:00
abstract::In the accompanying paper we constructed a model for the proliferation and differentiation of granulocyte-macrophage progenitor cells in response to the specific proliferation/differentiation stimulus granulocyte-macrophage colony-stimulating activity (gm-CSA). Here we have tested the model without altering the model ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::Granulocyte colony-stimulating factor (G-CSF) is used routinely in the clinical setting to mobilize hematopoietic stem progenitor cells (HSPCs) into the patient's blood for collection and subsequent transplantation. However, a significant proportion of patients who have previously received chemotherapy or radiotherapy...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2017.05.004
更新日期:2017-08-01 00:00:00
abstract::We have investigated the effect of hematopoietic cytokines on the survival of severe combined immune-deficient (SCID) mice that received a high dose of radiation. In this study, female SCID mice were irradiated at doses ranging from 500 to 600 cGy and then transplanted with 2 x 10(6) male Balb/c marrow cells. Groups o...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-02-01 00:00:00
abstract::We detail a novel, sensitive, and reproducible in vitro bioassay for erythropoietin that can be performed conveniently in any laboratory and is well suited for analysis of large numbers of samples. The assay measures DNA synthesis by a cohort of highly erythropoietin-responsive red cell precursors appearing in bone ma...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
abstract::Pretreatment of mice with 5-fluorouracil (5-FU) depletes total marrow cellularity but leaves a residual population of cells with enhanced regenerative capability. Using the long-term Dexter liquid culture system, we studied the effects of 5-FU on murine marrow cells and their production of pluripotent stem cells (CFU-...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-03-01 00:00:00
abstract:OBJECTIVE:To examine the possibility of adoptive cellular immunotherapy such as donor lymphocyte infusion using ex vivo expanded cord blood (CBL) lymphocytes, the potential expansion ability of CBL lymphocytes and the function of expanded CBL lymphocytes were evaluated. MATERIALS AND METHODS:Mononuclear cell fractions...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00776-2
更新日期:2002-04-01 00:00:00
abstract::Marrow obtained from mice (referred to as [X + BM] mice) 3 months after gamma-irradiation (9 Gy) and bone marrow inoculation (0.1 femur equivalents) showed a reduced capacity to reconstitute hemopoiesis of irradiated mice and an increased sensitivity to 5-fluorouracil. Sorting of marrow from (X + BM) mice on the basis...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::We have previously reported that granulocyte-macrophage colony-stimulating factor (GM-CSF) given after the administration of 5-fluorouracil (5-FU) results in augmented hematopoietic recovery as evidenced by increased white blood cell and neutrophil counts. Mice receiving GM-CSF following 5-FU administration were obser...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
abstract::The proliferative capacity of partially purified populations of mouse bone marrow progenitor cells has been examined in serum-free cultures in the presence and absence of colony-stimulating factors (CSFs). The half-life of progenitor cells was approximately 25 h in the absence of factor, regardless of whether the fact...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract::In vitro treatment of parental C57BL/6 lymphohematopoietic cell grafts with unabsorbed guinea pig anti-mouse thymocyte serum (ATS) and guinea pig complement (GPC), prior to inoculation into lethally irradiated B6D2F hybrid hosts, has proven to be of value in terms of mitigating graft-versus-host disease (GvHD). Howeve...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1976-11-01 00:00:00
abstract::The recent cloning of thrombopoietin (TPO) has allowed us to study its in vivo effects in normal and myelosuppressed mice. Normal Balb/c mice were treated with recombinant human TPO (hTPO) at doses ranging from 1 to 20 kU for 7 days, and complete blood counts (CBCs) and the number of megakaryocytes in the bone marrow ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::The development of pluripotential hematopoietic stem cells (PHSC) requires the continuous support provided by the bone tissue and bone marrow (BM) stromal cells. The basic rule of spatial and temporal organization of the distinct stromal cells and differentiating hematopoietic cells in the course of development, regen...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00