Abstract：
:Hematopoietic stem cell transplantation (HSCT) is an established treatment for multiple myeloma (MM), a plasma cell malignancy. To identify an improved pretransplant conditioning regimen, we investigated the cytotoxicity of gemcitabine (Gem) and clofarabine (Clo) combinations toward MM cell lines and patient cell samples. A strong synergism of the two nucleoside analogs, when combined at their approximate IC10 concentrations, was observed. This synergism could be partly due to the observed Gem-mediated phosphorylation and activation of deoxycytidine kinase, resulting in enhanced phosphorylation of Gem and Clo. Their cytotoxicity correlated with a robust activation of the DNA damage response pathway. [Gem+Clo] decreased the mitochondrial membrane potential with a concomitant release of proapoptotic factors into the cytoplasm and nucleus and the activation of apoptosis. Exposure of MM cells to [Gem+Clo] also decreased the level of ribosomal RNA (rRNA), which might have resulted in nucleolar stress, as reported previously, and caused a p53-dependent cell death. A reduction by approximately 50% in the cytotoxicity of Gem and Clo was observed in the presence of pifithrin α, a p53 inhibitor. Furthermore, MM cell lines with mutant p53 exhibited greater resistance to Gem and Clo, supporting a role for the p53 protein in these cytotoxic responses. Our results provide a rationale for clinical trials incorporating [Gem+Clo] combinations as part of conditioning therapy for high-risk patients with MM undergoing HSCT.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Valdez BC,Wang G,Murray D,Nieto Y,Li Y,Shah J,Turturro F,Wang M,Weber DM,Champlin RE,Qazilbash MH,Andersson BSdoi
10.1016/j.exphem.2013.04.009subject
Has Abstractpub_date
2013-08-01 00:00:00pages
719-30issue
8eissn
0301-472Xissn
1873-2399pii
S0301-472X(13)00201-4journal_volume
41pub_type
杂志文章abstract：:Classical studies of the developing embryo first suggested the existence of the hemangioblast, a precursor cell with the potential to differentiate into both blood and blood vessels. Several lines of investigation demonstrated that many of the genes activated during early hematopoietic development are also expressed i...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2003.07.001
更新日期：2003-11-01 00:00:00
abstract：:Hematopoiesis in continuous bone marrow culture is dependent upon close-range interaction between hematopoietic cells and marrow-derived adherent cells. The latter have been shown to include a significant proportion of fibroblastic elements, synthesizing the attachment protein fibronectin. The role of fibronectin in c...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-02-01 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：:Washed canine platelets were shown to express a significant level of von Willebrand factor (vWf). Canine platelet vWf differed from canine plasma vWf by the absence of satellite bands associated with each multimer when resolved by SDS-agarose gel electrophoresis. Expression and multimeric composition of canine platele...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:Cell surface molecules aberrantly expressed or overexpressed by myeloid leukemic cells represent potential disease-specific therapeutic targets for antibodies. MUC1 is a polymorphic glycoprotein, the cleavage of which yields two unequal chains: a large extracellular α subunit containing a tandem repeat array bound in ...
journal_title：Experimental hematology
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doi：10.1016/j.exphem.2018.12.002
更新日期：2019-02-01 00:00:00
abstract：:Sustained NF-κB activation is often observed in acute myeloid leukemia (AML); therefore, proteasome inhibition has been proposed to efficiently target AML cells. In this study, we questioned whether leukemic stem cell-enriched CD34(+) cells are sensitive to the proteasome inhibitor bortezomib. Surprisingly, we observe...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2013.02.002
更新日期：2013-06-01 00:00:00
abstract：:A method for growing erythroid bursts from rat bone marrow cells is presented. The methylcellulose culture technique with rat spleen-conditioned medium was used. Successful growth of rat BFU-E was obtained with 20% fetal bovine serum when anemic rat plasma was used as the source of erythropoietin. Plating efficiency w...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:To help establish an effective gene therapy protocol for patients with congenital metabolic diseases, we evaluated retrovirus-mediated transduction and long-term (LT) expression of the NeoR gene in cryopreserved and thawed CD34+ cells purified from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blo...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1997-08-01 00:00:00
abstract：:The pool size of erythroid burst-(BFUe) and colony-forming units (CFUe) has been evaluated in normal or hypoxia-induced polycythemic mice at sequential times after either transfusion or administration of purified erythropoietin (Ep). The present investigations were focused on the in vitro tritiated thymidine (3H-TdR) ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-01-01 00:00:00
abstract：OBJECTIVE:Among Philadelphia chromosome-negative myeloproliferative neoplasms (Ph(-) MPN), essential thrombocythemia (ET) and the prefibrotic phase of primary myelofibrosis (PMF) represent two subtypes with considerable overlap. MATERIALS AND METHODS:In this study, histopathological classification of 490 MPN cases was...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2009.07.005
更新日期：2009-10-01 00:00:00
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journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:Cancer stem cells (CSCs), including leukemia stem cells (LSCs), exhibit self-renewal capacity and differentiation potential and have the capacity to maintain or renew and propagate a tumor/leukemia. The initial isolation of CSCs/LSCs was in adult myelogenous leukemia, although more recently, the existence of CSCs in a...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
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更新日期：2017-08-01 00:00:00
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journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.11.013
更新日期：2008-04-01 00:00:00
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journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2016.02.005
更新日期：2016-06-01 00:00:00
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journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2013.11.012
更新日期：2014-02-01 00:00:00
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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
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journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2020.12.003
更新日期：2021-01-14 00:00:00
abstract：:Germinal center-associated nuclear protein (GANP) is a unique and multifunctional protein that plays a critical role in cell biology, neurodegenerative disorders, immunohematology, and oncogenesis. GANP is an orthologue of Saccharomyces Sac3, one of the components of the transcription export 2 (TREX-2) complex and a m...
journal_title：Experimental hematology
pub_type： 杂志文章,评审
doi：10.1016/j.exphem.2020.08.007
更新日期：2020-10-01 00:00:00
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journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.01.015
更新日期：2008-07-01 00:00:00
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journal_title：Experimental hematology
pub_type： 临床试验,杂志文章
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更新日期：2008-04-01 00:00:00
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journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-01-01 00:00:00
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journal_title：Experimental hematology
pub_type： 杂志文章,评审
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更新日期：2016-04-01 00:00:00
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journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-09-01 00:00:00
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journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-05-01 00:00:00
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journal_title：Experimental hematology
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doi：10.1016/j.exphem.2007.02.012
更新日期：2007-05-01 00:00:00
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journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1987-02-01 00:00:00
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journal_title：Experimental hematology
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doi：10.1016/j.exphem.2017.01.001
更新日期：2017-05-01 00:00:00
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journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1975-11-01 00:00:00
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journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-08-01 00:00:00
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journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1988-01-01 00:00:00
