Abstract：
:14-3-3 proteins are a family of master regulators of intracellular signaling, yet their impact on proteasome function is unknown. We demonstrate that 14-3-3ζ binds the 11S proteasome activator, limiting proteasome assembly and cellular capacity for protein degradation. To define the functional impact of 14-3-3ζ proteasomal binding in myeloma cells, silencing and overexpression experiments are performed. We find that downregulation of 14-3-3ζ impairs myeloma cell growth and confers resistance to clinically used proteasome inhibitors. In a large cohort of newly diagnosed myeloma patients, elevated expression of 14-3-3ζ is associated with high risk myeloma genetic subtypes and worse prognosis overall. Our work demonstrates the important role of 14-3-3ζ in regulating proteasome function, myeloma cell growth and sensitivity to therapeutics, and suggests regulation of 14-3-3ζ as a new approach in myeloma therapy.
journal_name
Leukemiajournal_title
Leukemiaauthors
Gu Y,Xu K,Torre C,Samur M,Barwick BG,Rupji M,Arora J,Neri P,Kaufman J,Nooka A,Bernal-Mizrachi L,Vertino P,Sun SY,Chen J,Munshi N,Fu H,Kowalski J,Boise LH,Lonial Sdoi
10.1038/leu.2017.288subject
Has Abstractpub_date
2018-03-01 00:00:00pages
744-751issue
3eissn
0887-6924issn
1476-5551pii
leu2017288journal_volume
32pub_type
杂志文章相关文献
LEUKEMIA文献大全abstract：:max 41 transgenic mice consistently exhibit elevated numbers of mature granulocytes and monocytes in the peripheral blood and of immature and mature cells of these lineages in the marrow, spleen, lymph nodes and liver. The immature populations are not autonomous and exhibit a normal quantitative responsiveness to prol...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1996-02-01 00:00:00
abstract：:Analysis at the DNA and RNA level revealed a mature genetic marker profile in a case of T type blast crisis of chronic myelocytic leukemia. T cell receptor beta chain gene rearrangement as well as T cell receptor alpha mRNA transcription was demonstrated in blasts of the malignant clone. Corresponding findings were ob...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1988-03-01 00:00:00
abstract：:In a 56-year-old male patient, receiving chemotherapy after radical surgery for bladder carcinoma, an unusual type of cytoplasmic inclusion was discovered in about 30% of peripheral blood lymphocytes. This was a single, large (about 2 microns in diameter), round or ovoid body, darker than the nucleus and reddish-viole...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1994-12-01 00:00:00
abstract：:In this study, fluorescence in situ hybridization (ISH) with an alphoid probe was used for the detection of trisomy 8 on archival blood smears (BS). The results were compared with hybridization experiments performed on methanol/acetic acid fixed cells of cytogenetic preparations (CP) which are widely used for ISH. Fiv...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：:Retroviral insertional mutagenesis in BXH2 mice commonly induces myeloid leukemias. One of the most frequently involved genes in experimental studies is Meis 1. In contrast to other genes in murine models, Meis 1 has not been affected by recurrent chromosomal translocations or point mutations in human leukemias. We fo...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2403377
更新日期：2004-07-01 00:00:00
abstract：:Translocations involving the immunoglobulin loci are recurring events of B cell oncogenesis. The majority of translocations involve the immunoglobulin heavy chain (IGH) locus, while a minor part involves the immunoglobulin light chain loci consisting of the kappa light chain (IGK) located at 2p11.2 and the lambda ligh...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2402648
更新日期：2002-10-01 00:00:00
abstract：:Multiple myeloma is the second most frequent hematological cancer after lymphoma and remains an incurable disease. The pervasive support provided by the bone marrow microenvironment to myeloma cells is crucial for their survival. Here, an unbiased assessment of receptor tyrosine kinases overexpressed in myeloma identi...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/s41375-019-0486-9
更新日期：2020-01-01 00:00:00
abstract：:Oncoprotein 18 (Op18) is a major cystolic phosphoprotein constituent of leukemia cells. There is cumulative evidence that suggests a role for Op18 in integrating signals from diverse pathways involved in cell growth. Op18 phosphorylation is induced with proliferation in a variety of cell types, and is essential for ce...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2400792
更新日期：1997-10-01 00:00:00
abstract：:Early molecular response is associated with improved probability of deep molecular response and superior survival in patients with CML-CP. However, ~1 in 3 patients on first-line imatinib do not achieve this threshold. The phase 2b DASCERN trial (NCT01593254) assessed the outcome of early switch to dasatinib in patien...
journal_title：Leukemia
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1038/s41375-020-0805-1
更新日期：2020-08-01 00:00:00
abstract：:It has been suggested that abnormalities of chromosome 3 at bands q21 and q26 are associated with the presence of increased numbers of abnormal megakaryocytes in patients with hematologic malignancies. The pretreatment bone marrows of 287 patients with leukemia (acute myeloid leukemia (AML), 225 patients; acute lympho...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
abstract：:East Asians, Asian Indians and Amerindians have a five to ten-fold lower age-adjusted incidence rate (AAIR) of chronic lymphocytic leukaemia (CLL) compared with persons of predominately European descent. The data we review suggest a genetic rather than environmental basis for this discordance. All these populations ar...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/s41375-020-01057-5
更新日期：2020-10-19 00:00:00
abstract：:The adult marrow hematopoietic stem cell biology has largely been based on studies of highly purified stem cells. This is unfortunate because during the stem cell purification the great bulk of stem cells are discarded. These cells are actively proliferating. The final purified stem cell is dormant and not representat...
journal_title：Leukemia
pub_type： 杂志文章,评审
doi：10.1038/leu.2017.155
更新日期：2017-08-01 00:00:00
abstract：:Cytogenetic and fluorescence in situ hybridization studies have shown the presence of telomeric repeats in translocation present in three patients with hematopoietic malignancies. One had jumping translocations, involving 1q12 and 2q, 16p, and 19q. These sequences were detected by FISH only in derivative chromosomes t...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401876
更新日期：2000-09-01 00:00:00
abstract：:The t(9;11)(p22;q23) is the most common chromosomal translocation in topoisomerase II inhibitor therapy-related acute myeloid leukemia (tAML). This translocation fuses the MLL and AF9 proto-oncogenes producing a novel chimeric protein. In order to gain insight into the mechanism generating the t(9;11) and to clarify t...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401223
更新日期：1998-12-01 00:00:00
abstract：:The outcome of a cohort of 218 consecutive patients who failed to respond to a single course of standard daunorubicin plus ARAC (three + seven) induction regimen has been retrospectively evaluated to assess the characteristics of this group of AML patients and the effectiveness of second-line induction programs. Seven...
journal_title：Leukemia
pub_type： 临床试验,杂志文章,多中心研究
doi：
更新日期：1996-09-01 00:00:00
abstract：:Targeted therapies are frequently combined with standard cytotoxic drugs to enhance clinical response. Targeting the B-cell lymphoma 2 (BCL-2) family of proteins is an attractive option to combat chemoresistance in leukemia. Preclinical and clinical studies indicate modest single-agent activity with selective BCL-2 in...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/leu.2017.243
更新日期：2018-02-01 00:00:00
abstract：:We have analyzed the expression of Tdt and CD7 in 335 cases of unequivocal acute myeloid leukemia (AML). Tdt was expressed in 80 (25%) of 321 evaluable cases. Twenty-six of 77 (34%) Tdt+ patients assessable for response, entered complete remission (CR) vs 121 of 209 (58%) Tdt- cases (P < 0.001). CD7 was expressed in 1...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401067
更新日期：1998-07-01 00:00:00
abstract：:The presence of rare malignant stem cells supplying a hierarchy of malignant cells has recently been reported. In human acute myelogenous leukemia (AML), the leukemia stem cells (LSCs) have been phenotypically restricted within the CD34+CD38- fraction. To understand the origin of malignant cells in primary human B-pre...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/leu.2008.83
更新日期：2008-06-01 00:00:00
abstract：:All-trans-retinoic (ATRA) treatment of patients with acute promyelocytic leukemia results in differentiation of the malignant cells and a high complete remission rate. ATRA treatment induced granulocytic differentiation in HL-60 cells as assessed by nitroblue tetrazolium (NBT) reduction, but had no effect on non-speci...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1993-03-01 00:00:00
abstract：:Surface phenotypes and genotypes of six T cell lines established from four patients with adult T cell leukemia (ATL) were compared with those of fresh ATL cells. The surface antigen densities of CD3 and T cell receptor (TCR) complex examined by OKT3 and WT-31 mAbs on fresh ATL cells were low. But three IL-2-dependent ...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1988-11-01 00:00:00
abstract：:Calicheamicin-conjugated humanized anti-CD33 mouse monoclonal antibody, CMA-676, has recently been introduced to clinics as a promising drug to treat patients with acute myeloid leukemia (AML) in relapse. However, the mechanism of action of CMA-676 has not been well elucidated. The cytotoxic effect of CMA-676 on HL60,...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401851
更新日期：2000-08-01 00:00:00
abstract：:The authors analyzed twelve patients with symptomatic essential throthrombocythemia (E.T.) diagnosed from 1983 to 1991. Haemorrhagic and thrombotic phenomena were the main presenting features. Treatment consisted mostly of alpha-interferon (IFN-alpha 2b) subcutaneously in dosage ranging from 3 to 5 MU/m2 and hydroxyur...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1992-01-01 00:00:00
abstract：:The 2001 World Health Organization (WHO) treatise on the classification of hematopoietic tumors lists chronic myeloproliferative diseases (CMPDs) as a subdivision of myeloid neoplasms that includes the four classic myeloproliferative disorders (MPDs)-chronic myelogenous leukemia, polycythemia vera (PV), essential thro...
journal_title：Leukemia
pub_type： 杂志文章,评审
doi：10.1038/sj.leu.2404955
更新日期：2008-01-01 00:00:00
abstract：:In a study carried out for patients receiving intrafamilial HLA-A,B,DR identical, MLC negative bone marrow transplants, RFLP profiles of HLA-class II for 27 donor recipient pairs were analyzed. Twenty-four pairs were found HLA-class II identical while three pairs were HLA-DP incompatible. The patients of these three p...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:Neutropenia-related fungal infections can be life-threatening despite antifungal therapy. We evaluated the role of recombinant granulocyte colony-stimulating factor (rG-CSF)-elicited white blood cell (WBC) transfusions in patients with neutropenia-related fungal infections. Adult patients with hematologic malignancies...
journal_title：Leukemia
pub_type： 临床试验,杂志文章
doi：10.1038/sj.leu.2400811
更新日期：1997-10-01 00:00:00
abstract：:It has been proposed that adoptive immunotherapy, for the treatment of relapsed AML, with cytotoxic T lymphocytes which show a relative specificity for the leukemic cells may have the advantage of maximizing the beneficial anti-leukemic effect whilst minimizing the probability of graft-versus-host disease. In this stu...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2402013
更新日期：2001-02-01 00:00:00
abstract：:Resistant AML encompasses two groups of patients: those with refractory leukemia and those whose leukemia has relapsed. Refractory leukemia is disease that does not respond to initial induction chemotherapy with cytarabine and an anthracycline. Patients with refractory leukemia are likely to have disease with adverse ...
journal_title：Leukemia
pub_type： 杂志文章,评审
doi：
更新日期：1998-09-01 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Leukemia
pub_type： 已发布勘误
doi：10.1038/s41375-020-0782-4
更新日期：2020-09-01 00:00:00
abstract：:Ikaros family zinc finger protein 1 and 3 (IKZF1 and IKZF3) are transcription factors that promote multiple myeloma (MM) proliferation. The immunomodulatory imide drug (IMiD) lenalidomide promotes myeloma cell death via Cereblon (CRBN)-dependent ubiquitylation and proteasome-dependent degradation of IKZF1 and IKZF3. A...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/s41375-019-0403-2
更新日期：2019-08-01 00:00:00
abstract：:Two pediatric cases of acute lymphoblastic leukemia with L1 morphology who also demonstrated immunoglobulin on the leukemic cell surface are presented. The first patient's disease progressed on standard induction therapy, despite the presence of good prognostic features at presentation. The second patient has achieved...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1988-01-01 00:00:00
