Abstract：
:Specific myeloid-related and inositide-specific gene mutations can be linked to myelodysplastic syndromes (MDS) pathogenesis and therapy. Here, 44 higher-risk MDS patients were treated with azacitidine and lenalidomide and mutations analyses were performed at baseline and during the therapy. Results were then correlated to clinical outcome, overall survival (OS), leukemia-free-survival (LFS) and response to therapy. Collectively, 34/44 patients were considered evaluable for response, with an overall response rate of 76.25% (26/34 cases): 17 patients showed a durable response, 9 patients early lost response and 8 patients never responded. The most frequently mutated genes were ASXL1, TET2, RUNX1, and SRSF2. All patients early losing response, as well as cases never responding, acquired the same 3 point mutations during therapy, affecting respectively PIK3CD (D133E), AKT3 (D280G), and PLCG2 (Q548R) genes, that regulate cell proliferation and differentiation. Moreover, Kaplan-Meier analyses revealed that this mutated cluster was significantly associated with a shorter OS, LFS, and duration of response. All in all, a common mutated cluster affecting 3 inositide-specific genes is significantly associated with loss of response to azacitidine and lenalidomide therapy in higher risk MDS. Further studies are warranted to confirm these data and to further analyze the functional role of this 3-gene cluster.
journal_name
Leukemiajournal_title
Leukemiaauthors
Follo MY,Pellagatti A,Armstrong RN,Ratti S,Mongiorgi S,De Fanti S,Bochicchio MT,Russo D,Gobbi M,Miglino M,Parisi S,Martinelli G,Cavo M,Luiselli D,McCubrey JA,Suh PG,Manzoli L,Boultwood J,Finelli C,Cocco Ldoi
10.1038/s41375-019-0416-xsubject
Has Abstractpub_date
2019-09-01 00:00:00pages
2276-2290issue
9eissn
0887-6924issn
1476-5551pii
10.1038/s41375-019-0416-xjournal_volume
33pub_type
杂志文章相关文献
LEUKEMIA文献大全abstract：:Data on outcome in older (≥70 years) patients with acute promyelocytic leukemia after treatment with arsenic trioxide (ATO) compared with standard chemotherapy (CTX) is scarce. We evaluated 433 patients (median age, 73.4 years) treated either with ATO+ all-trans retinoic acid (ATO/ATRA; n = 26), CTX/ATRA + ATO during ...
journal_title：Leukemia
pub_type： 杂志文章,多中心研究
doi：10.1038/s41375-020-0758-4
更新日期：2020-09-01 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：:The majority of neutralizing antibodies of HTLV-I are directed against linear epitopes of the envelope surface glycoprotein (gp46) in the immunodominant region 175-199. Although gp46 presents a remarkable degree of conservation, the substitution of the proline at position 192 by a serine is described for 10 isolates a...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1997-04-01 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：:The Brazilian Cooperative Group for Treatment of Childhood Acute Lymphocytic Leukemia (GBTLI) has started clinical activities trials in 1980. Three consecutive multicenter studies in children with unprevious treated ALL have been completed including 994 patients. The first GBTLI-80 accrued 203 children from 1980 to 19...
journal_title：Leukemia
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：
更新日期：1993-08-01 00:00:00
abstract：:B-cell acute lymphoblastic leukemia (B-ALL) is often associated with chromosomal translocations leading to the deregulation of proto-oncogenes. MicroRNAs can also be affected by chromosomal alterations and thus contribute to carcinogenesis. The microRNA, miR-125b-1, is overexpressed in B-ALL cases with the t(11;14)(q2...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/leu.2012.95
更新日期：2012-10-01 00:00:00
abstract：:The molecular basis for autonomous growth of malignant forms of human T lymphocytes is not known. It can be investigated by functional responses of malignant cells in comparison with untransformed counterparts. At least two pathways (the CD2 and CD3 pathways) of human T-cell activation have been recently defined on th...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1992-06-01 00:00:00
abstract：:Secondary chromosomal aberrations reported in the literature were surveyed in acute myeloid or lymphoblastic leukemia (AML or ALL) with one of the following primary abnormalities: in AML, t(1;3), t(1;22), der(1;7), inv(3), t(3;5) +4, del(5q), t(6;9), -7, t(7;11), del(7q), +8, t(8;16), t(8;21), +9, t(9;11), del(9q), t(...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1994-06-01 00:00:00
abstract：:An antisense oligodeoxynucleotide (ODN) complementary to the first six codons of the Bcl-2 mRNA, G3139 (oblimersen sodium; Genasense), has been shown to downregulate Bcl-2 and produce responses in a variety of malignancies including drug-resistant lymphoma. Incubation of ex vivo purified plasma cells from patients wit...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2402768
更新日期：2003-01-01 00:00:00
abstract：:The effect of deoxycytidine (dCyd) on the inhibitory effects of two antileukemic nucleoside analogs, 5-aza-2'-deoxycytidine and ara-5-aza-Cyd, toward the clonogenic growth of normal human bone marrow progenitors (CFU-GM) and leukemic blast progenitors (L-CFU) was examined. Continuous exposure of cells to 10(-6)-10(-5)...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1987-12-01 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：:The altered metabolism of cancer cells is a treasure trove to discover new antitumoral strategies. The gene (SLC7A5) encoding system L amino-acid transporter 1 (LAT1) is overexpressed in murine lymphoma cells generated via T-cell deletion of the pten tumor suppressor, and also in human T-cell acute lymphoblastic leuke...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/leu.2014.338
更新日期：2015-06-01 00:00:00
abstract：:Human promonocytic cell line U937 cells can be induced to differentiate into macrophages by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA treatment induced the expression of the monocytic differentiation markers CD11b and CD36, with concomitant morphological changes. Moreover, TPA enhanced reactive ox...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/leu.2008.353
更新日期：2009-04-01 00:00:00
abstract：:The effects of retinoic acid (RA) on the cell growth and expression of interleukin-2 (IL-2) receptors (IL-2R alpha/p55, Tac, CD25) by the human T lymphotropic virus type I (HTLV-I)-positive T cell lines, HUT102 and ATL-2 were investigated. Incubation of these cells for 48 h with either 13-cis retinoid acid (13-cis RA)...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2400593
更新日期：1997-03-01 00:00:00
abstract：:Immunoglobulin (IG) gene repertoire restrictions strongly support antigen selection in the pathogenesis of chronic lymphocytic leukemia (CLL). Given the emerging multifarious interactions between CLL and bystander T cells, we sought to determine whether antigen(s) are also selecting T cells in CLL. We performed a larg...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/leu.2016.362
更新日期：2017-07-01 00:00:00
abstract：:This paper describes seven patients with ALL and a hypodiploid karyotype with less than 40 chromosomes. A consideration of these and 15 previously published cases indicates that they may be divided into two groups depending on chromosome number, i.e., less than 30 and 30-39. The less than 30 group are younger and pred...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
abstract：:Seventeen cytogenetic laboratories in eight European countries contributed karyotypic, hematological, clinical and follow-up data from 550 patients with an acquired abnormality of 11q23. The patients had acute lymphoblastic leukemia (254), acute myeloid leukemia (250), unspecified, undifferentiated, biphenotypic acute...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2401011
更新日期：1998-05-01 00:00:00
abstract：:The clinical and cell growth characteristics of 11 children with monosomy 7 presenting as preleukemia (eight cases) or acute nonlymphoblastic leukemia (three cases) were studied. Anemia was common to all patients, with nine showing leukocytosis, seven thrombocytopenia, and one thrombocytosis. There was a striking pred...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1987-02-01 00:00:00
abstract：:Since hemopoietic cells are refractory to transfection by conventional chemical means, we have developed a reliable and efficient gene transfer system for K562 cells which uses electric field-mediated gene transfer (EFMGT). EFMGT involves the exposure of cells in suspension to an electric field which transiently allow...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
abstract：:Disruption of pathways leading to programmed cell death plays a major role in most malignancies, including multiple myeloma (MM). ABT-737 is a BH3 mimetic small-molecule inhibitor that binds with high affinity to Bcl-2 and Bcl-xL, preventing the sequestration of proapoptotic molecules and shifting the cell survival/ap...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2404719
更新日期：2007-07-01 00:00:00
abstract：:The notion that inherited predisposition contributes to the development of haematological malignancies is generally thought of as being a relatively new idea. However, Videbaek made a clear enunciation of such a hypothesis in 1947, from a study of tumour incidence in relatives of patients with different leukaemias. To...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2403727
更新日期：2005-06-01 00:00:00
abstract：:Acute myelogenous leukemia (AML) remains a deadly disease for most adult patients, due primarily to the emergence of chemoresistant cells. Defects in apoptosis pathways make important contributions to chemoresistance, suggesting a need to restore apoptosis sensitivity or to identify alternative pathways for apoptosis ...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2403112
更新日期：2003-11-01 00:00:00
abstract：:We used fluorescence in situ hybridization (FISH) to metaphase chromosomes with BCR and ABL cosmid probes in conjunction with the polymerase chain reaction (PCR) to study the mechanism by which the ABL proto-oncogene is inserted into a morphologically normal chromosome 22 in patients with Ph-negative chronic myeloid l...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
abstract：:Viral infection induces potent cellular immunity and activated intracellular signaling, which may dictate the driver events involved in immune escape and clonal selection of virus-associated cancers, including Epstein-Barr virus (EBV)-positive lymphomas. Here, we thoroughly interrogated PD-L1/PD-L2-involving somatic a...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/s41375-019-0380-5
更新日期：2019-07-01 00:00:00
abstract：:The p53 tumor suppressor gene is frequently mutated within its evolutionarily conserved regions in a number of human cancers. Previous reports demonstrated mutations of this gene in both Burkitt's lymphoma and B cell chronic lymphocytic leukemia. However, dissimilar results were obtained in non-Hodgkin's lymphoma (NHL...
journal_title：Leukemia
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:Glucocorticoid (GC) receptor (GR) phosphorylation and signature genes were studied in chronic lymphocytic leukemia (CLL) cells to help place GCs within modern treatment algorithms. In contrast to normal B and T cells, transcription of GC-regulated genes was not rhythmic and the synthetic GC dexamethasone (DEX) could n...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/s41375-019-0381-4
更新日期：2019-07-01 00:00:00
abstract：:Multidrug resistance (MDR), a significant impediment to the successful treatment of cancer clinically, has been attributed to the overexpression of P-glycoprotein (P-gp), a plasma membrane multidrug efflux transporter. P-gp maintains sublethal intracellular drug concentrations by virtue of its drug efflux capacity. Th...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/leu.2009.76
更新日期：2009-09-01 00:00:00
abstract：:The AML1 is the most commonly involved transcription factor gene in human leukemias and forms chimeric transcription factor genes, namely, AML1/MTG8 by the t(8;21), AML1/EVI-1 by the t(3;21), and TEL/AML1 by the t(12;21). The AML1a and AML1b, two isoforms of the AML1 protein, are translated from the AML1 gene by the a...
journal_title：Leukemia
pub_type： 杂志文章,评审
doi：
更新日期：1997-04-01 00:00:00
abstract：:Kinase inhibitors block proliferative signals in BCR-ABL1+ leukemic cells, but their capacity to induce apoptosis is poorly understood. Initial studies suggested that very brief exposure to kinase inhibitors was sufficient to induce apoptosis in chronic myeloid leukemia (CML) cells. However, flaws in this experimental...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/leu.2014.156
更新日期：2015-01-01 00:00:00
abstract：:Both conventional chimerism analysis (CCA) and lineage-specific chimerism analysis (LCA) have potential pitfalls as diagnostic means for the detection of minimal residual disease after allogeneic hematopoietic cell transplantation (aHCT). Therefore, the present study examines the results of both methods in order to de...
journal_title：Leukemia
pub_type： 杂志文章
doi：10.1038/sj.leu.2403719
更新日期：2005-05-01 00:00:00
