Abstract:
:Activation of the MEK/ERK/MAP kinase signaling pathway promotes the proliferation and survival of hematopoietic cells. The kinases MEK-1, MEK-2, ERK-1/MAPK and ERK-2/MAPK are activated by phosphorylation at specific sites, and these events can be monitored using phospho-specific antibodies. In this report we examined the importance of the MEK/ERK/MAP kinase pathway in the monocytic and granulocytic differentiation of myeloid cell lines. Induction of monocytic differentiation in HL-60 cells by treatment with phorbol 12-myristate 13-acetate (PMA) led to rapid and sustained activation of MEK-1/-2, ERK-1/MAPK and ERK-2/MAPK, while induction of granulocytic differentiation by retinoic acid (RA) caused similar activation of MEK-1/-2 and ERK-2/MAPK, but not ERK-1/MAPK. The total levels of these kinases were not affected during the course of differentiation along either pathway. Pretreatment of cells with 5 microM of the MEK-1/-2-specific inhibitor U0126 abrogated PMA- or RA-induced activation of ERK-1/MAPK and ERK-2/MAPK. Importantly, pretreatment of HL-60 cells with U0126 was found to potently inhibit both monocytic and granulocytic differentiation, as assessed by cytochemical staining for non-specific esterase or nitroblue tetrazolium reduction, flow cytometric analysis of myeloid surface markers, and immunoblotting for the cell cycle inhibitor p21 WAF1/Cip1. Similar results were seen in U937 cells, where U0126 inhibited PMA-induced monocytic differentiation, and in 32D cells, where G-CSF-induced granulocytic differentiation was inhibited by U0126 pretreatment. Additional experiments revealed that inhibition of MEK-1/-2 in HL-60 cells resulted in nearly complete inhibition of differentiation-induced cell death during monocytic differentiation. By contrast, U0126 only partially inhibited cell death resulting from granulocytic differentiation. Taken together, our findings demonstrate that the MEK/ERK/MAP kinase signaling pathway is activated, and plays a critical role, during both monocytic and granulocytic differentiation of myeloid cell lines.
journal_name
Leukemiajournal_title
Leukemiaauthors
Miranda MB,McGuire TF,Johnson DEdoi
10.1038/sj.leu.2402400subject
Has Abstractpub_date
2002-04-01 00:00:00pages
683-92issue
4eissn
0887-6924issn
1476-5551journal_volume
16pub_type
杂志文章相关文献
LEUKEMIA文献大全abstract::Although current treatments can induce clinical complete remissions in the vast majority of patients with indolent lymphoma, most of them actually relapse, because of the persistence of residual tumor cells which are undetectable using conventional diagnostic procedures. Polymerase chain reaction (PCR)-based methods a...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2401559
更新日期:1999-11-01 00:00:00
abstract::The T-lineage phenotype in children with acute lymphoblastic leukaemia (ALL) is associated with in vitro drug resistance and a higher relapse-risk compared to a precursor B phenotype. Our study was aimed to investigate whether mutations in the ATM gene occur in childhood T-lineage acute lymphoblastic leukaemia (T-ALL)...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403943
更新日期:2005-11-01 00:00:00
abstract::CD79 is a heterodimeric molecule comprising two polypeptide chains, B29 (CD79b) and mb-1 (CD79a). It is physically linked in the surface of B cells to membrane immunoglobulin, forming the B cell antigen receptor complex. Expression of the mb-1 (CD79a) chain has been studied in leukaemias and shown to be present in mos...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::Syk is a protein tyrosine kinase that couples B-cell receptor (BCR) activation with downstream signaling pathways, affecting cell survival and proliferation. Moreover, Syk is involved in BCR-independent functions, such as B-cell migration and adhesion. In chronic lymphocytic leukemia (CLL), Syk becomes activated by ex...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2012.24
更新日期:2012-07-01 00:00:00
abstract::In order to improve leukemia-free survival (LFS) without the treatment-related morbidity of allogeneic bone marrow transplantation or multiple prolonged cycles of consolidation chemotherapy, we evaluated the long-term outcome of autologous transplantation of peripheral blood progenitor cells (PBPCs) as postremission t...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403126
更新日期:2003-11-01 00:00:00
abstract::Mesenchymal stromal cells (MSCs) possess broad immunomodulatory capacities that are currently investigated for potential clinical application in treating autoimmune disorders. Third-party MSCs suppress alloantigen-induced proliferation of peripheral blood mononuclear cells providing the rationale for clinical use in g...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2014.273
更新日期:2014-12-01 00:00:00
abstract::An unambiguous case of Sèzary syndrome associated with the presence of unusual retroviral infection markers is described. The blood smear showed 15% typical Sèzary cells but also rare atypical lymphocytes with convoluted nuclei, evocative of characteristic adult T-cell leukemia (ATL) flower cells. However, the patient...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::The expression of myeloid surface markers was investigated in 41 cases of untreated adult acute lymphoblastic leukemia (ALL). Nineteen cases (46%) reacted with at least one myeloid monoclonal antibody (CD15 in 16 cases, CD13 in 10 cases, CD14 in five cases, and CD33 in four cases). Double-staining confirmed the coexpr...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1990-09-01 00:00:00
abstract::GM-CSF transgenic mice were crossed with mice with homozygous inactivation of the gene encoding the common beta chain (beta c) of the GM-CSF receptor to produce mice with constitutively elevated GM-CSF levels but no high-affinity GM-CSF receptors. GM-CSF transgenic beta c -/- mice had exceptionally elevated serum GM-C...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2400926
更新日期:1998-03-01 00:00:00
abstract::Human DNA ligase was purified from different kinds of immunocompetent cells: thymocytes, normal and stimulated lymphocytes, blasts from ALL (Burkitt and non-T, non-B) and ANLL (M1, M2, and M5). Based upon the protocol for the treatment of these leukemias, the purified enzymes were assayed in the presence of routinely ...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
abstract::Acute graft-versus-host disease (aGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (alloHCT) and is a major cause of morbidity and mortality. Systemic steroid therapy is the first-line treatment for aGVHD, although about half of patients will become refractory to treatment. As the n...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/s41375-020-0804-2
更新日期:2020-05-01 00:00:00
abstract::The polymerase chain reaction (PCR) cannot be used to amplify the breakpoint in the chimaeric BCR-ABL gene in CML and acute leukaemias due to the large variation in the sites of breakpoint in the BCR gene (within a 5.8 kb region) and in the ABL gene (within a 150 kb region). The disease state is usually monitored usin...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::Improved survival of patients with acute lymphoblastic leukemia (ALL) has emerged from identifying new prognostic markers; however, 20% of children still suffer recurrence. Previously, the altered expression of Fat1 cadherin has been implicated in a number of solid tumors. In this report, in vitro analysis shows that ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2011.319
更新日期:2012-05-01 00:00:00
abstract::PRDM1/BLIMP-1, a master regulator of plasma-cell differentiation, is frequently inactivated in activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) patients. Little is known about its genetic aberrations and relevant clinical implications. A large series of patients with de novo DLBCL was effectively eval...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2016.243
更新日期:2017-03-01 00:00:00
abstract::Interleukin-4 inhibits several monocyte functions like A23187-induced expression of cytokines and c-fos and c-jun proto-oncogene mRNA expression. In an attempt to elucidate the mechanism by which this inhibitive effect is mediated, we compared the effect of IL-4 on A23187-induced c-fos and c-jun mRNA expression in con...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::CDCP1, a novel stem cell marker, is expressed in hematopoietic cell line K562 but not in Jurkat. When CDCP1 promoter was transfected exogenously, Jurkat showed comparable promoter activity with K562, suggesting that the factor to enhance transcription was present but interfered to function in Jurkat. The reporter assa...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404312
更新日期:2006-09-01 00:00:00
abstract::Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 fro...
journal_title:Leukemia
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/leu.2015.281
更新日期:2016-03-01 00:00:00
abstract::The lysozyme (LZM) gene provides a very useful model for studies of phagocyte maturation, because its protein synthesis is increased during myelopoiesis and thus most abundant in terminally differentiated and activated phagoyctes. LZM gene expression and DNA methylation were examined in various normal and transformed ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2400693
更新日期:1997-07-01 00:00:00
abstract::In this study, we determined the respective roles of RelA and RelB NF-κB subunits in Epstein-Barr virus (EBV)-transformed B cells. Using different EBV-immortalized B-cell models, we showed that only RelA activation increased both survival and cell growth. RelB activity was induced secondarily to RelA activation and re...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2013.274
更新日期:2014-04-01 00:00:00
abstract::Acute myeloid leukemia (AML) is a heterogeneous disease with multiple different cytogenetic and molecular aberrations contributing to leukemic transformation. We compared gene expression profiles of 4608 genes using cDNA-arrays from 20 AML patients (nine with -7/del7q and 11 with normal karyotype) with 23 CD34+ prepar...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404093
更新日期:2006-03-01 00:00:00
abstract::Eventually, gene therapy may be a valid option for chronic viral infections, including retroviral infections. Human retroviral diseases fit two categories: (1) those that result from a monoclonal outgrowth of a human T-cell leukemia virus type I (HTLV-I)-infected cell, as in the case of adult T cell leukemia (ATL); an...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:
更新日期:1995-10-01 00:00:00
abstract::A patient with the M2 subtype of AML who had a 45,X,-X,t(8;21) karyotype at diagnosis was found to have the Ph chromosome in one out of 37 evaluated cells 18 months after the initial diagnosis. Interphase FISH studies utilizing a BCR-ABL dual-color probe did not detect a fusion product 4 months prior to the appearance...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2400974
更新日期:1998-04-01 00:00:00
abstract::The inv(16)(p13q22) chromosomal rearrangement associated with FAB M4Eo acute myeloid leukemia (AML) subtype is characterized by the presence of the CBFbeta/MYH11 fusion transcript that can be used to detect minimal residual disease (MRD). However, qualitative RT-PCR studies of MRD have so far produced conflicting resu...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2402478
更新日期:2002-06-01 00:00:00
abstract::Mobilizing bone cells to the head, astutely referred to as 'bonehead' therapeutic approach, represents a major discipline of regenerative medicine. The last decade has witnessed mounting evidence supporting the capacity of bone marrow (BM)-derived cells to mobilize from BM to peripheral blood (PB), eventually finding ...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/leu.2011.167
更新日期:2011-11-01 00:00:00
abstract::Bortezomib is a potent drug for the treatment of multiple myeloma. Its anti-tumor activity is mediated by proteasome inhibition leading to decreased cell proliferation and induction of apoptosis. However, an unimpaired proteasomal function plays a crucial role for the induction of anti-tumor immunity by dendritic cell...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404734
更新日期:2007-07-01 00:00:00
abstract::A human acute lymphoblastic leukemia (ALL) cell line, BALM-9, was established from the peripheral blood specimen of a immunoglobin (lg) phenotype, the established BALM-9 cell line expressed both kappa and lambda light (L) chains simultaneously in a range of 30-80%. Two-color flow cytometric analysis demonstrated that ...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::Single kinase-targeted cancer therapies often failed prolonged responses because cancer cells bypass through alternative routes. In this study, high-throughput kinomic and proteomic approaches enabled to identify aberrant activity profiles in mixed lineage leukemia (MLL)-rearranged acute myeloid leukemia (AML) that de...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2013.342
更新日期:2014-03-01 00:00:00
abstract::Natural killer (NK) cell-type lymphoproliferative diseases of granular lymphocytes can be subdivided into aggressive NK cell leukemia (ANKL) and chronic NK cell lymphocytosis (CNKL). One reason for the poor outcome in ANKL is leukemic infiltration into multiple organs. The mechanisms of cell trafficking associated wit...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403732
更新日期:2005-07-01 00:00:00
abstract::Imatinib has pronounced antileukemic activity in Ph+ALL, although responses are usually short. To determine whether imatinib may facilitate allogeneic SCT in relapsed or refractory Ph+ALL, we evaluated 46 consecutive, not previously transplanted patients who were enrolled in phase II studies of imatinib. Of 30 patient...
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:10.1038/sj.leu.2402770
更新日期:2002-12-01 00:00:00
abstract::The FMS-like tyrosine kinase-3 (FLT3) gene is the most commonly mutated gene in acute myeloid leukemia (AML), and patients carrying internal tandem duplication (ITD) mutations have a poor prognosis. Long-term inhibition of FLT3 activity in these patients has been elusive. To provide a more complete understanding of FL...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2016.284
更新日期:2017-03-01 00:00:00