Abstract:
:Large granular lymphocyte leukemia (LGLL) is a rare and chronic lymphoproliferative disorder characterized by the clonal expansion of LGLs. LGLL patients can be asymptomatic or develop cytopenia, mostly neutropenia. Somatic STAT3 and STAT5b mutations have been recently reported in approximately 40% of patients. The aim of this study is to analyze clinical and biological features of a large cohort of LGLL patients to identify prognostic markers affecting patients' outcome. In 205 LGLL patients, neutropenia (ANC < 1500/mm3) was the main feature (38%), with severe neutropenia (ANC < 500/mm3) being present in 20.5% of patients. STAT3 mutations were detected in 28.3% patients and were associated with ANC < 500/mm3 (p < 0.0001), Hb < 90 g/L (p = 0.0079) and treatment requirement (p < 0.0001) while STAT5b mutations were found in 15/152 asymptomatic patients. By age-adjusted univariate analysis, ANC < 500/mm3 (p = 0.013), Hb < 90 g/L (p < 0.0001), treatment requirement (p = 0.001) and STAT3 mutated status (p = 0.011) were associated to reduced overall survival (OS). By multivariate analysis, STAT3 mutated status (p = 0.0089) and Hb < 90 g/L (p = 0.0011) were independently associated to reduced OS. In conclusion, we identified clinical and biological features associated to reduced OS in LGLL and we demonstrated the adverse impact of STAT3 mutations in patients' survival, suggesting that this biological feature should be regarded as a potential target of therapy.
journal_name
Leukemiajournal_title
Leukemiaauthors
Barilà G,Teramo A,Calabretto G,Vicenzetto C,Gasparini VR,Pavan L,Leoncin M,Vedovato S,Frigo AC,Facco M,Semenzato G,Zambello Rdoi
10.1038/s41375-019-0644-0subject
Has Abstractpub_date
2020-04-01 00:00:00pages
1116-1124issue
4eissn
0887-6924issn
1476-5551pii
10.1038/s41375-019-0644-0journal_volume
34pub_type
临床试验,杂志文章相关文献
LEUKEMIA文献大全abstract::In diffuse large B-cell lymphoma (DLBCL), the clinical and biological significance of concordant and discordant bone marrow (BM) involvement have not been well investigated. We evaluated 712 de novo DLBCL patients with front-line rituximab-containing treatment, including 263 patients with positive and 449 with negativ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2017.222
更新日期:2018-02-01 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::Highly polymorphic tandemly repetitive DNA sequences provide powerful genetic markers for the identification of individuals by restriction fragment length polymorphisms (RFLP) even in close relatives. Over a three-year period, 61 consecutive patients from a single institution undergoing allogeneic bone marrow transpla...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::We evaluated the synergistic activity of AS101 (ammonium trichloro-(dioxoethylene-0-0')-tellurate) with the protein kinase C (PKC) activators, Bryostatin-1 and phorbol-12-myristate-13-acetate (PMA), on human myelocytic leukemia cell differentiation in vitro, and in a mouse model. Use of AS101 with Bryostatin-1 or with...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404746
更新日期:2007-07-01 00:00:00
abstract::The Wilms' tumor 1 (WT1) gene encodes a transcription factor important for normal cellular development and cell survival. The initial discovery of WT1 as the causative gene in an autosomal-recessive condition identified it as a tumor suppressor gene whose mutations are associated with urogenital disease and the develo...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2404624
更新日期:2007-05-01 00:00:00
abstract::A mutational analysis of the delta region of the Jun protein shows an inverse correlation between transforming and transactivation potential of the mutant proteins if both properties are measured in chicken embryo fibroblasts. The possibility that Jun acquires oncogenicity not by gain but by loss of function is also s...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Acute myeloid leukemia (AML) with 11q23/MLL rearrangement (MLL-r AML) is allocated to the intermediate- or high-risk cytogenetic prognostic category depending on the MLL fusion partner. A more favorable outcome has been reported in patients receiving an allogeneic hematopoietic stem-cell transplantation (alloHSCT), bu...
journal_title:Leukemia
pub_type: 杂志文章,多中心研究
doi:10.1038/leu.2015.143
更新日期:2015-12-01 00:00:00
abstract::Several tyrosine kinases such as Jak1, Jak3, Lck and Syk are known to participate in IL-2-mediated intracellular signal transduction. Jak1, Lck and Syk are associated with the cytoplasmic domain of the beta chain, whereas Jak3 is associated with the cytoplasmic domain of the gamma chain, which is shared among receptor...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::To examine whether the percentage of myeloperoxidase (MPO)-positive blast cells is useful as a prognostic factor for acute myeloid leukemia (AML), cytochemical analysis of MPO was performed in 491 patients who were registered to the Japan Adult Leukemia Study Group-AML92 study. Patients were divided into two using the...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2403010
更新日期:2003-08-01 00:00:00
abstract::Patients with normal-karyotype acute myelogenous leukemia (NKAML) may have undetected genetic abnormalities that could affect prognosis. Screening for known AML-specific genetic abnormalities using the reverse transcription polymerase chain reaction (RT-PCR) may help in arriving at a more definitive prognosis. To test...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401951
更新日期:2001-01-01 00:00:00
abstract::HOX homeobox proteins are key oncogenic drivers in hematopoietic malignancies. Here we demonstrate that HOXA1, HOXA6 and predominantly HOXA9 are able to induce the production of insulin-like growth factor 1 (Igf1). In chromatin immunoprecipitations, HOXA9 bound directly to the putative promoter and a DNase-hypersensit...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2014.287
更新日期:2015-04-01 00:00:00
abstract::Myelodysplastic syndrome (MDS) in children is often considered as a variant of acute myeloid leukemia (AML) and frequently treated as such. However, there are very few reported data on the outcome following AML treatment. We analyzed 20 consecutive cases of de novo MDS treated in Denmark according to the NOPHO AML pro...
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::We previously reported a strong IL4I1 gene expression in primary mediastinal B-cell lymphoma (PMBL) and recently identified the protein as a secreted L-phenylalanine oxidase, physiologically expressed by myeloid cells, which inhibits T-cell proliferation in vitro. Here, we analyzed the pattern of IL4I1 protein express...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2008.380
更新日期:2009-05-01 00:00:00
abstract::The role of endothelial progenitor cell (EPC)-mediated vasculogenesis in hematological malignancies is not well explored. Here, we showed that EPCs are mobilized from the bone marrow (BM) to the peripheral blood at early stages of multiple myeloma (MM); and recruited to MM cell-colonized BM niches. Using EPC-defective...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2016.3
更新日期:2016-05-01 00:00:00
abstract::The chromosomal inversion (16)(p13q22), which is associated with the M4-eosinophilia subtype of human acute myeloid leukemia, causes the fusion of two distinct genes. The polypeptide encoded by the chimeric gene, PEBP2p/CBFp-SMMHC, retains the ability to interact with, and dominantly interfere with the function of pro...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401821
更新日期:2000-07-01 00:00:00
abstract::Transplantation of normal and malignant human hematopoietic cells into severe combined immunodeficient (SCID) mice allows for evaluation of long-term growth abilities of these cells and provides a preclinical model for therapeutic interventions. However, large numbers of cells are required for successful engraftment i...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2400694
更新日期:1997-07-01 00:00:00
abstract::Although dephosphorylation of tyrosine containing proteins is considered a necessary step in the induction of leukemia cell differentiation by hybrid polar compounds (HPC), the crucial actors in this step remain unknown. We present evidence that tyrosine phosphorylation of JAK1 and JAK2 is down-regulated in murine ery...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401936
更新日期:2000-12-01 00:00:00
abstract::Smoldering multiple myeloma (SMM) is a biologically heterogeneous, clinically defined entity with a variable rate of progression to symptomatic multiple myeloma (MM). Reliable markers for progression are critical for the development of potential therapeutic interventions. We retrospectively evaluated the predictive va...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/s41375-018-0013-4
更新日期:2018-06-01 00:00:00
abstract::To guide development of new clinical strategies, a review of recent investigations in the pathobiology of MDS was performed. Articles were identified through a Medline search. Studies, including reviews, are cited in the references. A multistep pathogenesis is proposed. (1) Targeted injury or mutation within hemopoiet...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:10.1038/sj.leu.2401618
更新日期:2000-01-01 00:00:00
abstract::We have investigated the protective effect of human T-cell leukemia virus I (HTLV-I) immune globulin (HTLVIG) against HTLV-I in rabbits. HTLVIG containing 77 mg/ml of IgG was prepared from pooled plasma from seropositive healthy persons. In the first experiment, four groups (A, B, C, and D) of three rabbits were trans...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Previous studies in pediatric patients with acute myelogenous leukemia (AML) have suggested that 2-chlorodeoxyadenosine (2CdA) is an effective therapeutic agent. Santana et al (J Clin Oncol 1992; 10: 364-370) reported a CR rate of 8/17 (95% Cl 23-72%) in children with relapsed AML and a median first CR of 21 months. T...
journal_title:Leukemia
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::A 32-year-old white woman was admitted with a diagnosis of T lymphoblastic lymphoma and a bone marrow and peripheral blood cytology that was suggestive of a myeloproliferative syndrome (MPS). In addition, islets of myeloid precursors were found in the lymph node where the lymphoma had been diagnosed. Cytogenetic exami...
journal_title:Leukemia
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract::Mantle cell lymphoma represent a clinicopathologically distinct entity of malignant non-Hodgkin's lymphoma (NHL) and are characterized by a specific chromosomal translocation t(11;14)(q13;q32) involving the cyclin D1 gene also designated as bcl-1/PRAD1 gene on chromosome 11 and the heavy chain immunoglobulin joining r...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401172
更新日期:1998-10-01 00:00:00
abstract::It is apparent that treatment of Hodgkin's disease can be complicated by the development of secondary leukaemia. Most such leukaemias are of the non-lymphocytic type. We describe here a patient treated for Hodgkin's disease with chemo- and radiotherapy who developed secondary acute lymphoblastic leukaemia with a non-r...
journal_title:Leukemia
pub_type: 杂志文章,评审
doi:
更新日期:1991-07-01 00:00:00
abstract::In this study, we compared immunoglobulin heavy-chain-gene-based minimal residual disease (MRD) detection by real-time quantitative PCR (RQ-PCR) and next-generation sequencing (NGS) to assess whether NGS could overcome some limitations of RQ-PCR and further increase sensitivity, specificity, accuracy and reproducibili...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/leu.2013.375
更新日期:2014-06-01 00:00:00
abstract::De novo acute myeloid leukemia (AML) with dysplastic features in erythroblasts, granulocytes and megakaryocytes, similar to those in myelodysplastic syndrome (MDS) has been described as AML with trilineage dysplasia (AML-TLD) since 1987. Several reports have suggested that AML-TLD is a subtype of de novo AML in adults...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2401924
更新日期:2000-11-01 00:00:00
abstract::We assessed the epidemiologic progress against childhood and adolescent acute lymphoblastic leukaemia (ALL) in the Netherlands over a 26 year period. ALL patients <18 years were selected from the Netherlands Cancer Registry and the Dutch Childhood Oncology Group. Trend analyses were performed over time and by age grou...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/s41375-020-01024-0
更新日期:2020-08-21 00:00:00
abstract::We have carried out a high-resolution whole genome DNA profiling analysis on 100 bone marrow samples from a consecutive series of de novo acute myeloid leukemia (AML) cases. After discarding copy number changes that are known to be genetic polymorphisms, we found that genomic aberrations (GA) in the form of gains or l...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404653
更新日期:2007-06-01 00:00:00
abstract::A widely accepted definition of resistance or intolerance to hydroxyurea (HU) in patients with essential thrombocythemia (ET) is lacking. An international working group (WG) was convened to develop a consensus formulation of clinically significant criteria for defining resistance/intolerance to HU in ET. To this aim, ...
journal_title:Leukemia
pub_type: 杂志文章
doi:10.1038/sj.leu.2404473
更新日期:2007-02-01 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