Clonal evolution in relapsed NPM1-mutated acute myeloid leukemia.

Abstract:

:Mutations in the nucleophosmin 1 (NPM1) gene are considered a founder event in the pathogenesis of acute myeloid leukemia (AML). To address the role of clonal evolution in relapsed NPM1-mutated (NPM1mut) AML, we applied high-resolution, genome-wide, single-nucleotide polymorphism array profiling to detect copy number alterations (CNAs) and uniparental disomies (UPDs) and performed comprehensive gene mutation screening in 53 paired bone marrow/peripheral blood samples obtained at diagnosis and relapse. At diagnosis, 15 aberrations (CNAs, n = 10; UPDs, n = 5) were identified in 13 patients (25%), whereas at relapse, 56 genomic alterations (CNAs, n = 46; UPDs, n = 10) were detected in 29 patients (55%) indicating an increase in genomic complexity. Recurrent aberrations acquired at relapse included deletions affecting tumor suppressor genes (ETV6 [n = 3], TP53 [n = 2], NF1 [n = 2], WT1 [n = 3], FHIT [n = 2]) and homozygous FLT3 mutations acquired via UPD13q (n = 7). DNMT3A mutations (DNMT3Amut) showed the highest stability (97%). Persistence of DNMT3Amut in 5 patients who lost NPM1mut at relapse suggests that DNMT3Amut may precede NPM1mut in AML pathogenesis. Of note, all relapse samples shared at least 1 genetic aberration with the matched primary AML sample, implying common ancestral clones. In conclusion, our study reveals novel insights into clonal evolution in NPM1mut AML.

journal_name

Blood

journal_title

Blood

authors

Krönke J,Bullinger L,Teleanu V,Tschürtz F,Gaidzik VI,Kühn MW,Rücker FG,Holzmann K,Paschka P,Kapp-Schwörer S,Späth D,Kindler T,Schittenhelm M,Krauter J,Ganser A,Göhring G,Schlegelberger B,Schlenk RF,Döhner H,Döhner K

doi

10.1182/blood-2013-01-479188

subject

Has Abstract

pub_date

2013-07-04 00:00:00

pages

100-8

issue

1

eissn

0006-4971

issn

1528-0020

pii

blood-2013-01-479188

journal_volume

122

pub_type

杂志文章

相关文献

BLOOD文献大全
  • A rapid assay for evaluation of iron-chelating agents in rats.

    abstract::The animal assay of potential new iron-chelating agents is at present dependent on cumbersome and imprecise iron balance studies in hypertransfused rodents. We report the development of a radioisotope assay in intact rats based on the transient labeling by ferritin 59Fe of the main source of chelatable iron within hep...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Pippard MJ,Johnson DK,Finch CA

    更新日期:1981-10-01 00:00:00

  • Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production.

    abstract::Interleukin-33 (IL-33), a member of the IL-1 cytokine family, is emerging as a new regulator of immune responses and inflammatory vascular diseases. Although IL-33 and its cognate receptor ST2 appear to be expressed in vascular cells, the precise role of IL-33 in the vasculature has not been determined. In this study,...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-02-203372

    authors: Choi YS,Choi HJ,Min JK,Pyun BJ,Maeng YS,Park H,Kim J,Kim YM,Kwon YG

    更新日期:2009-10-01 00:00:00

  • Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome-positive leukemia.

    abstract::Although imatinib, a BCR-ABL tyrosine kinase inhibitor, is used to treat acute Philadelphia chromosome-positive (Ph(+)) leukemia, it does not prevent central nervous system (CNS) relapses resulting from poor drug penetration through the blood-brain barrier. Imatinib and dasa-tinib (a dual-specific SRC/BCR-ABL kinase i...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:10.1182/blood-2008-02-140665

    authors: Porkka K,Koskenvesa P,Lundán T,Rimpiläinen J,Mustjoki S,Smykla R,Wild R,Luo R,Arnan M,Brethon B,Eccersley L,Hjorth-Hansen H,Höglund M,Klamova H,Knutsen H,Parikh S,Raffoux E,Gruber F,Brito-Babapulle F,Dombret H,Dua

    更新日期:2008-08-15 00:00:00

  • ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice.

    abstract::A prominent feature of sickle cell anemia is the presence of dehydrated red blood cells (RBCs) in circulation. Loss of potassium (K(+)), chloride (Cl(-)), and water from RBCs is thought to contribute to the production of these dehydrated cells. One main route of K(+) loss in the RBC is the Gardos channel, a calcium (C...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-05-1433

    authors: Stocker JW,De Franceschi L,McNaughton-Smith GA,Corrocher R,Beuzard Y,Brugnara C

    更新日期:2003-03-15 00:00:00

  • CD33 expression and P-glycoprotein-mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapy.

    abstract::Gemtuzumab ozogamicin (GO) contains an anti-CD33 antibody to facilitate uptake of a toxic calicheamicin-gamma(1) derivative. While recent in vitro data demonstrated a quantitative relationship between CD33 expression and GO cytotoxicity, previous correlative studies failed to identify a significant association between...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-09-047399

    authors: Walter RB,Gooley TA,van der Velden VH,Loken MR,van Dongen JJ,Flowers DA,Bernstein ID,Appelbaum FR

    更新日期:2007-05-15 00:00:00

  • Expression of p53 in human leukemia and lymphoma.

    abstract::Analysis of fresh human tumors have indicated that patients with B type lymphoproliferative diseases and the majority of patients with acute lymphoblastic leukemia (ALL) express elevated levels of p53 production. It is suggested that in these human malignancies, p53 may provide a novel tool for monitoring cancer activ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Prokocimer M,Shaklai M,Bassat HB,Wolf D,Goldfinger N,Rotter V

    更新日期:1986-07-01 00:00:00

  • Characterization of endogenous cytokine concentrations after high-dose chemotherapy with autologous bone marrow support.

    abstract::Endogenous cytokines are thought to mediate numerous biologic processes and may account for some adverse effects experienced following the administration of recombinant proteins. This study describes the pattern of endogenous cytokine exposure following high-dose chemotherapy. Blood concentrations of interleukin-6 (IL...

    journal_title:Blood

    pub_type: 临床试验,杂志文章

    doi:

    authors: Rabinowitz J,Petros WP,Stuart AR,Peters WP

    更新日期:1993-05-01 00:00:00

  • Matching at the MHC class I K locus is essential for long-term engraftment of purified hematopoietic stem cells: a role for host NK cells in regulating HSC engraftment.

    abstract::The events that regulate engraftment and long-term repopulating ability of hematopoietic stem cells (HSCs) after transplantation are not well defined. We report for the first time that major histocompatibility complex (MHC) class I K plays a critical role in HSC engraftment via interaction with recipient natural kille...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-11-3910

    authors: Huang Y,Rezzoug F,Chilton PM,Grimes HL,Cramer DE,Ildstad ST

    更新日期:2004-08-01 00:00:00

  • Definitive but not primitive hematopoiesis is impaired in jumonji mutant mice.

    abstract::A novel gene, jumonji was identified by a mouse gene trap strategy. The jumonji gene encodes a protein containing a putative DNA binding domain. The mice homozygous for jumonji gene with a BALB/cA genetic background show hypoplasia of the fetal liver and embryonic lethality, suggesting impaired hematopoiesis. In the p...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kitajima K,Kojima M,Nakajima K,Kondo S,Hara T,Miyajima A,Takeuchi T

    更新日期:1999-01-01 00:00:00

  • Transduction of CLL cells by CD40 ligand enhances an antigen-specific immune recognition by autologous T cells.

    abstract::Several features of chronic lymphocytic leukemia (CLL) suggest that immune-based strategies may have therapeutic potential. A promising approach is provided by the transduction of CLL cells with CD40 ligand (CD40L) by viral vectors to enhance their immunogenicity. We compared the antigen-presenting capacity of CD40L-t...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-04-1742

    authors: Mayr C,Kofler DM,Büning H,Bund D,Hallek M,Wendtner CM

    更新日期:2005-11-01 00:00:00

  • Only the CD62L+ subpopulation of CD4+CD25+ regulatory T cells protects from lethal acute GVHD.

    abstract::CD4+CD25+ regulatory T (Treg) cells are potent modulators of alloimmune responses. In murine models of allogeneic bone marrow transplantation, adoptive transfer of donor CD4+CD25+ Treg cells protects recipient mice from lethal acute graft-versus-host disease (aGVHD) induced by donor CD4+CD25- T cells. Here we examined...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-05-2044

    authors: Ermann J,Hoffmann P,Edinger M,Dutt S,Blankenberg FG,Higgins JP,Negrin RS,Fathman CG,Strober S

    更新日期:2005-03-01 00:00:00

  • Clinical relevance of point mutations in the cytoplasmic domain of the granulocyte colony-stimulating factor receptor gene in patients with severe congenital neutropenia.

    abstract::Recently, point mutations in the gene of the granulocyte colony-stimulating factor (G-CSF) receptor have been reported in two patients with severe congenital neutropenia who developed acute myeloid leukemia (AML). We investigated the frequency of these specific G-CSF receptor mutations in patients with congenital neut...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Tidow N,Pilz C,Teichmann B,Müller-Brechlin A,Germeshausen M,Kasper B,Rauprich P,Sykora KW,Welte K

    更新日期:1997-04-01 00:00:00

  • Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells.

    abstract::Interleukin (IL)-23 is a proinflammatory cytokine belonging to the IL-12 superfamily. The antitumor activity of IL-23 is controversial, and it is unknown whether or not the cytokine can act directly on tumor cells. The aim of this study was to investigate the potential direct antitumor activity of IL-23 in pediatric B...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-10-248245

    authors: Cocco C,Canale S,Frasson C,Di Carlo E,Ognio E,Ribatti D,Prigione I,Basso G,Airoldi I

    更新日期:2010-11-11 00:00:00

  • An insertional mutagenesis screen identifies genes that cooperate with Mll-AF9 in a murine leukemogenesis model.

    abstract::Patients with a t(9;11) translocation (MLL-AF9) develop acute myeloid leukemia (AML), and while in mice the expression of this fusion oncogene also results in the development of myeloid leukemia, it is with long latency. To identify mutations that cooperate with Mll-AF9, we infected neonatal wild-type (WT) or Mll-AF9 ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-04-281428

    authors: Bergerson RJ,Collier LS,Sarver AL,Been RA,Lugthart S,Diers MD,Zuber J,Rappaport AR,Nixon MJ,Silverstein KA,Fan D,Lamblin AF,Wolff L,Kersey JH,Delwel R,Lowe SW,O'Sullivan MG,Kogan SC,Adams DJ,Largaespada DA

    更新日期:2012-05-10 00:00:00

  • The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice.

    abstract::Although recent advances have enabled hematopoietic stem cells (HSCs) to be enriched to near purity, more information about their characteristics will improve our understanding of their development and stage-related functions. Here, using microarray technology, we identified endothelial cell-selective adhesion molecul...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-07-167106

    authors: Yokota T,Oritani K,Butz S,Kokame K,Kincade PW,Miyata T,Vestweber D,Kanakura Y

    更新日期:2009-03-26 00:00:00

  • Mast cells produce interleukin-25 upon Fc epsilon RI-mediated activation.

    abstract::Interleukin-25 (IL-25) is a recently described T helper 2 (T(H)2) cell-derived cytokine that belongs to the IL-17 family and induces the production of IL-4, IL-5, and IL-13 from an unidentified non-T-cell population. Here, we show that mast cells are also potent IL-25-producing cells. When bone marrow-derived mast cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-09-2817

    authors: Ikeda K,Nakajima H,Suzuki K,Kagami S,Hirose K,Suto A,Saito Y,Iwamoto I

    更新日期:2003-05-01 00:00:00

  • 15-Deoxy-delta 12,14-prostaglandin J2 induces apoptosis in human malignant B cells: an effect associated with inhibition of NF-kappa B activity and down-regulation of antiapoptotic proteins.

    abstract::Cyclopentenone prostaglandins are potent inhibitors of nuclear factor-kappa B (NF-kappa B), a transcription factor with a critical role in promoting inflammation and connected with multiple aspects of oncogenesis and cancer cell survival. In the present report, we investigated the role of NF-kappa B in the antineoplas...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-04-1360

    authors: Piva R,Gianferretti P,Ciucci A,Taulli R,Belardo G,Santoro MG

    更新日期:2005-02-15 00:00:00

  • Evidence for a multipotential stem cell disease in some childhood Philadelphia chromosome-positive acute lymphoblastic leukemia.

    abstract::Children with Philadelphia chromosome (Ph+) acute lymphoblastic leukemia (ALL) have a poorer prognosis than do most pediatric patients with ALL. Because of this poor prognosis and the presence of the Ph chromosome, we have asked whether or not Ph + ALL involves a multipotential stem cell. We cultured hematopoietic pro...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Tachibana N,Raimondi SC,Lauer SJ,Sartain P,Dow LW

    更新日期:1987-11-01 00:00:00

  • High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy.

    abstract::Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Brown RA,Herzig RH,Wolff SN,Frei-Lahr D,Pineiro L,Bolwell BJ,Lowder JN,Harden EA,Hande KR,Herzig GP

    更新日期:1990-08-01 00:00:00

  • Ligand-induced internalization selects use of common receptor neuropilin-1 by VEGF165 and semaphorin3A.

    abstract::Neuropilin-1 (Npn-1) is a receptor shared by class 3 semaphorins and heparin-binding forms of vascular endothelial growth factor (VEGF), protein families that regulate endothelial and neuronal-cell function. Ligand interaction with Npn-1 dictates the choice of signal transducer; plexins transduce semaphorin signals, a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-10-4113

    authors: Narazaki M,Tosato G

    更新日期:2006-05-15 00:00:00

  • Identification of BCR/ABL-negative primitive hematopoietic progenitor cells within chronic myeloid leukemia marrow.

    abstract::Chronic myeloid leukemia (CML) is a malignant disorder of the hematopoietic stem cell. It has been shown that normal stem cells coexist with malignant stem cells in the bone marrow of patients with chronic-phase CML. To characterize the primitive hematopoietic progenitor cells within CML marrow, CD34+DR- and CD34+DR+ ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Leemhuis T,Leibowitz D,Cox G,Silver R,Srour EF,Tricot G,Hoffman R

    更新日期:1993-02-01 00:00:00

  • CD148 is a membrane protein tyrosine phosphatase present in all hematopoietic lineages and is involved in signal transduction on lymphocytes.

    abstract::Evidence is presented showing that a protein tyrosine phosphatase different from CD45 is present on the membrane of human hematopoietic cells. The molecule recognized by the monoclonal antibody 143-41, which has been classified as CD148 in the VI International Workshop on Leukocyte Differentiation Antigens, was immuno...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: de la Fuente-García MA,Nicolás JM,Freed JH,Palou E,Thomas AP,Vilella R,Vives J,Gayá A

    更新日期:1998-04-15 00:00:00

  • Perforin deficiency impairs a critical immunoregulatory loop involving murine CD8(+) T cells and dendritic cells.

    abstract::Humans and mice with impaired perforin-dependent cytotoxic function may develop excessive T-cell activation and the fatal disorder hemophagocytic lymphohistiocytosis (HLH) after infection. Though cytotoxic lymphocytes can kill antigen-presenting cells, the physiological mechanism of perforin-mediated immune regulation...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-04-495309

    authors: Terrell CE,Jordan MB

    更新日期:2013-06-27 00:00:00

  • Selective suppression of IL-12 production by human herpesvirus 6.

    abstract::Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that has been suggested to act as a cofactor in the progression of HIV disease. Exposure of human macrophages to HHV-6A or HHV-6B profoundly impaired their ability to produce interleukin 12 (IL-12) upon stimulation with interferon-gamma (IFN-gamma) a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-10-3152

    authors: Smith A,Santoro F,Di Lullo G,Dagna L,Verani A,Lusso P

    更新日期:2003-10-15 00:00:00

  • Ferritin translation by interleukin-1and interleukin-6: the role of sequences upstream of the start codons of the heavy and light subunit genes.

    abstract::Interleukin-1beta (IL-1beta) elevates H- and L-ferritin subunit synthesis in both human hepatoma cells (HepG2) and primary human umbilical vein endothelial cells. Ferritin induction is greater than the increase in total HepG2 protein synthesis in response to IL-1. IL-6 causes a moderate increase in L-subunit synthesis...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Rogers JT

    更新日期:1996-03-15 00:00:00

  • Demonstration of Kaposi's sarcoma-associated herpes virus cyclin D homolog in cutaneous Kaposi's sarcoma by colorimetric in situ hybridization using a catalyzed signal amplification system.

    abstract::Kaposi's sarcoma-associated herpes virus (KSHV)/human herpes virus 8 (HHV8) DNA sequences have been demonstrated in Kaposi's sarcoma (KS), as well as in some acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphomas (NHL) and in multicentric Castleman's disease. Although KSHV DNA generally is abundant ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Reed JA,Nador RG,Spaulding D,Tani Y,Cesarman E,Knowles DM

    更新日期:1998-05-15 00:00:00

  • Gene expression profile in human leukocytes.

    abstract::Leukocytes are classified as myelocytic or lymphocytic, and each class of leukocytes consists of several types of cells that have different phenotypes and different roles. To define the gene expression in these cells, we have performed serial analysis of gene expression (SAGE) using human leukocytes and have provided ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-06-1866

    authors: Hashimoto S,Nagai S,Sese J,Suzuki T,Obata A,Sato T,Toyoda N,Dong HY,Kurachi M,Nagahata T,Shizuno K,Morishita S,Matsushima K

    更新日期:2003-05-01 00:00:00

  • Mouse RUNX1C regulates premegakaryocytic/erythroid output and maintains survival of megakaryocyte progenitors.

    abstract::RUNX1 is crucial for the regulation of megakaryocyte specification, maturation, and thrombopoiesis. Runx1 possesses 2 promoters: the distal P1 and proximal P2 promoters. The major protein isoforms generated by P1 and P2 are RUNX1C and RUNX1B, respectively, which differ solely in their N-terminal amino acid sequences. ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2016-06-723635

    authors: Draper JE,Sroczynska P,Leong HS,Fadlullah MZH,Miller C,Kouskoff V,Lacaud G

    更新日期:2017-07-20 00:00:00

  • Immunosuppression and other risk factors for early and late non-Hodgkin lymphoma after kidney transplantation.

    abstract::Non-Hodgkin lymphoma (NHL) incidence is greatly increased after kidney transplantation. NHL risk was investigated in a nationwide cohort of 8164 kidney transplant recipients registered on the Australia and New Zealand Dialysis and Transplant Registry. NHL diagnoses were ascertained using linkage with national cancer r...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-02-202507

    authors: van Leeuwen MT,Grulich AE,Webster AC,McCredie MR,Stewart JH,McDonald SP,Amin J,Kaldor JM,Chapman JR,Vajdic CM

    更新日期:2009-07-16 00:00:00

  • Identification of HIF2alpha as an important STAT5 target gene in human hematopoietic stem cells.

    abstract::The transcription factor signal transducer and activator of transcription 5 (STAT5) fulfills essential roles in self-renewal in mouse and human hematopoietic stem cells (HSCs), and its persistent activation contributes to leukemic transformation, although little molecular insight into the underlying mechanisms has bee...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-08-303669

    authors: Fatrai S,Wierenga AT,Daenen SM,Vellenga E,Schuringa JJ

    更新日期:2011-03-24 00:00:00