Distinct iron architecture in SF3B1-mutant myelodysplastic syndrome patients is linked to an SLC25A37 splice variant with a retained intron.

Abstract:

:Perturbation in iron homeostasis is a hallmark of some hematologic diseases. Abnormal sideroblasts with accumulation of iron in the mitochondria are named ring sideroblasts (RS). RS is a cardinal feature of refractory anemia with RS (RARS) and RARS with marked thrombocytosis (RARS/-T). Mutations in SF3B1, a member of the RNA splicing machinery are frequent in RARS/-T and defects of this gene were linked to RS formation. Here we showcase the differences in iron architecture of SF3B1-mutant and wild-type (WT) RARS/-T and provide new mechanistic insights by which SF3B1 mutations lead to differences in iron. We found higher iron levels in SF3B1 mutant vs WT RARS/-T by transmission electron microscopy/spectroscopy/flow cytometry. SF3B1 mutations led to increased iron without changing the valence as shown by the presence of Fe(2+) in mutant and WT. Reactive oxygen species and DNA damage were not increased in SF3B1-mutant patients. RNA-sequencing and Reverse transcriptase PCR showed higher expression of a specific isoform of SLC25A37 in SF3B1-mutant patients, a crucial importer of Fe(2+) into the mitochondria. Our studies suggest that SF3B1 mutations contribute to cellular iron overload in RARS/-T by deregulating SLC25A37.

journal_name

Leukemia

journal_title

Leukemia

authors

Visconte V,Avishai N,Mahfouz R,Tabarroki A,Cowen J,Sharghi-Moshtaghin R,Hitomi M,Rogers HJ,Hasrouni E,Phillips J,Sekeres MA,Heuer AH,Saunthararajah Y,Barnard J,Tiu RV

doi

10.1038/leu.2014.170

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

188-95

issue

1

eissn

0887-6924

issn

1476-5551

pii

leu2014170

journal_volume

29

pub_type

杂志文章

相关文献

LEUKEMIA文献大全
  • The vascular niche: home for normal and malignant hematopoietic stem cells.

    abstract::Hematopoietic stem cells (HSCs) are uniquely capable of self-renewal and provision of all of the mature elements of the blood and immune system throughout the lifetime of an individual. HSC self-renewal is regulated by both intrinsic mechanisms and extrinsic signals mediated via specialized microenvironments or 'niche...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/leu.2011.236

    authors: Doan PL,Chute JP

    更新日期:2012-01-01 00:00:00

  • Biologic response modifiers in acute lymphoblastic leukemia.

    abstract::Despite the presence of tumor antigens, the paucity of clinically significant T-cell mediated immune responses against human tumors is striking. This may, in part, be because of the inability of cancer cells to function as efficient antigen-presenting cells. For full activation, T cells must receive two signals delive...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:

    authors: Gribben JG,Cardoso AA,Schultze JL,Nadler LM

    更新日期:1997-05-01 00:00:00

  • IKZF1 deletion is an independent prognostic marker in childhood B-cell precursor acute lymphoblastic leukemia, and distinguishes patients benefiting from pulses during maintenance therapy: results of the EORTC Children's Leukemia Group study 58951.

    abstract::The added value of IKZF1 gene deletion (IKZF1(del)) as a stratifying criterion in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is still debated. We performed a comprehensive analysis of the impact of IKZF1(del) in a large cohort of children (n=1223) with BCR-ABL1-negative BCP-ALL treated in the EORTC-CLG tr...

    journal_title:Leukemia

    pub_type: 杂志文章,随机对照试验

    doi:10.1038/leu.2015.134

    authors: Clappier E,Grardel N,Bakkus M,Rapion J,De Moerloose B,Kastner P,Caye A,Vivent J,Costa V,Ferster A,Lutz P,Mazingue F,Millot F,Plantaz D,Plat G,Plouvier E,Poirée M,Sirvent N,Uyttebroeck A,Yakouben K,Girard S,Dastu

    更新日期:2015-11-01 00:00:00

  • Heterogeneity in protein patterns of cells from terminal blast crisis in chronic granulocytic leukemia: discrimination between lymphatic and myeloid lineages.

    abstract::Terminal blast crisis cells of chronic granulocytic leukemia are biochemically distinct. Triton-X-114 detergent phase lysates revealed that myeloid types express predominantly proteins of a 24 kd apparent molecular weight range, whereas lymphatic types do not express these molecules but a 55 kd protein band. These bio...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Doxiadis I,Dölken P,Schneider M,Wernet P,Grosse-Wilde H

    更新日期:1988-12-01 00:00:00

  • MEIS 1 expression is downregulated through promoter hypermethylation in AML1-ETO acute myeloid leukemias.

    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

    authors: Lasa A,Carnicer MJ,Aventín A,Estivill C,Brunet S,Sierra J,Nomdedéu JF

    更新日期:2004-07-01 00:00:00

  • Hypermethylation of the calcitonin gene in the myelodysplastic syndromes.

    abstract::It is well documented that the calcitonin gene area in the short arm of chromosome 11 is hypermethylated in most acute leukemias as well as in chronic lymphatic leukemia. In contrast, the gene is normally methylated during the chronic phase of the chronic myeloid leukemia but turns hypermethylated as the disease escal...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Ihalainen J,Pakkala S,Savolainen ER,Jansson SE,Palotie A

    更新日期:1993-02-01 00:00:00

  • Expression of CD1d by myelomonocytic leukemias provides a target for cytotoxic NKT cells.

    abstract::Natural killer T (NKT) cells with an invariant T-cell receptor for alpha-galactosylceramide (alphaGalCer) that is presented by CD1d have been reported to be cytotoxic for myelomonocytic leukemia cells. However, the necessity for leukemia cell CD1d expression, the role of alphaGalCer, and the cytotoxic mechanisms have ...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2402943

    authors: Metelitsa LS,Weinberg KI,Emanuel PD,Seeger RC

    更新日期:2003-06-01 00:00:00

  • Identification of CD34+ cells in normal and pathological bone marrow biopsies by QBEND10 monoclonal antibody.

    abstract::Monoclonal antibody QBEND10 is reactive with the CD34 antigen in aldehyde-fixed, decalcified, paraffin-embedded bone marrow biopsies. In normal bone marrow it stained endothelial cells lining arterioles and capillaries, sinusoidal (littoral) cells and 0.89% of all haemopoietic cells. QBEND10+ mononuclear cells were se...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Soligo D,Delia D,Oriani A,Cattoretti G,Orazi A,Bertolli V,Quirici N,Deliliers GL

    更新日期:1991-12-01 00:00:00

  • Clinical impact of minimal residual disease in children with different subtypes of acute lymphoblastic leukemia treated with Response-Adapted therapy.

    abstract::To determine the clinical significance of minimal residual disease (MRD) in patients with prognostically relevant subtypes of childhood acute lymphoblastic leukemia (ALL), we analyzed data from 488 patients treated in St Jude Total Therapy Study XV with treatment intensity based mainly on MRD levels measured during re...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2016.234

    authors: Pui CH,Pei D,Raimondi SC,Coustan-Smith E,Jeha S,Cheng C,Bowman WP,Sandlund JT,Ribeiro RC,Rubnitz JE,Inaba H,Gruber TA,Leung WH,Yang JJ,Downing JR,Evans WE,Relling MV,Campana D

    更新日期:2017-02-01 00:00:00

  • Dissecting the pathways to death.

    abstract::This report summarizes recent findings in the field of basic and translational apoptosis research which were presented at the 1st Conference on 'Mechanisms of Cell Death and Disease: Advances in Therapeutic Intervention' organized by the European School of Hematology and the University of Texas MD Anderson Cancer Cent...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/sj.leu.2401940

    authors: Daniel PT

    更新日期:2000-12-01 00:00:00

  • Antigen receptor stereotypy in chronic lymphocytic leukemia.

    abstract::The discovery of almost identical or 'stereotyped' B-cell receptor immunoglobulins (BcR IG) among unrelated patients with chronic lymphocytic leukemia (CLL) cemented the idea of antigen selection in disease ontogeny and evolution. The systematic analysis of the stereotypy phenomenon in CLL revealed that around one-thi...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/leu.2016.322

    authors: Stamatopoulos K,Agathangelidis A,Rosenquist R,Ghia P

    更新日期:2017-02-01 00:00:00

  • Refining the diagnosis of T-cell large granular lymphocytic leukemia by combining distinct patterns of antigen expression with T-cell clonality studies.

    abstract::T-cell large granular lymphocytic (LGL) leukemia is a complex diagnosis, requiring persistent clonal expansions of LGLs, and cytopenias. Often the diagnosis is unclear as non-clonal expansions of LGLs commonly occur in reactive conditions. To better understand T-LGL leukemia, we performed a comprehensive clinicopathol...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2011.107

    authors: Ohgami RS,Ohgami JK,Pereira IT,Gitana G,Zehnder JL,Arber DA

    更新日期:2011-09-01 00:00:00

  • Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia.

    abstract::Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2017.265

    authors: Toft N,Birgens H,Abrahamsson J,Griškevičius L,Hallböök H,Heyman M,Klausen TW,Jónsson ÓG,Palk K,Pruunsild K,Quist-Paulsen P,Vaitkeviciene G,Vettenranta K,Åsberg A,Frandsen TL,Marquart HV,Madsen HO,Norén-Nyström U,Schmi

    更新日期:2018-03-01 00:00:00

  • Telomere length is severely and similarly reduced in JAK2V617F-positive and -negative myeloproliferative neoplasms.

    abstract::Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized by chronic proliferation of hematopoietic progenitors. We studied the telomere length (TL) of 335 MPN patients and 93 gender- and age-matched controls using a quantitative PCR method (relative TL calculated as the ratio of the amount of t...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2008.319

    authors: Bernard L,Belisle C,Mollica L,Provost S,Roy DC,Gilliland DG,Levine RL,Busque L

    更新日期:2009-02-01 00:00:00

  • Role of catalase in monocytic differentiation of U937 cells by TPA: hydrogen peroxide as a second messenger.

    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

    authors: Yamamoto T,Sakaguchi N,Hachiya M,Nakayama F,Yamakawa M,Akashi M

    更新日期:2009-04-01 00:00:00

  • Intensive chemotherapy in childhood myelodysplastic syndrome. A comparison with results in acute myeloid leukemia.

    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:

    authors: Hasle H,Kerndrup G,Yssing M,Clausen N,Ostergaard E,Jacobsen N,Jacobsen BB

    更新日期:1996-08-01 00:00:00

  • Clinical significance of beta 2-microglobulin in serum of adult T cell leukemia.

    abstract::To clarify the clinical and biological significance of beta 2-microglobulin (beta 2-M) in serum of adult T cell leukemia (ATL) associated with human lymphotropic virus type-I (HTLV-I), beta 2-M was measured in 52 patients with ATL (acute ATL, 35 patients; lymphoma ATL, two patients; chronic ATL, 12 patients; smolderin...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Sadamori N,Mine M,Hakariya S,Ichiba M,Kawachi T,Itoyama T,Nakamura H,Tomonaga M,Hayashi K

    更新日期:1995-04-01 00:00:00

  • Action of interferons in hairy cell leukemia.

    abstract::We have investigated the direct effects of interferon (IFN) on hairy cells (HCs) isolated from patients with hairy cell leukemia using one- and two-dimensional gel electrophoresis. We have previously characterized the induction of synthesis of 10-16 specific proteins by IFN-alpha 2b in HCs, as analyzed by one-dimensio...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Samuels BL,Rosner MC,Giometti CS,Golomb HM,Brownstein BH

    更新日期:1987-04-01 00:00:00

  • Down-regulation of c-myc gene is not obligatory for growth inhibition and differentiation of human myeloid leukemia cells.

    abstract::Suppression of c-myc expression is observed during induced differentiation of several myeloid cell lines and it has been attributed to the cell growth arrest that accompanies terminal differentiation. To dissect the role of c-Myc in the proliferation-differentiation switch we have studied c-myc expression in K562 cell...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Gómez-Casares MT,Delgado MD,Lerga A,Crespo P,Quincoces AF,Richard C,León J

    更新日期:1993-11-01 00:00:00

  • Homing and mobilization of hematopoietic stem cells and hematopoietic cancer cells are mirror image processes, utilizing similar signaling pathways and occurring concurrently: circulating cancer cells constitute an ideal target for concurrent treatment wi

    abstract::Adhesion molecules and stromal cell-derived factor-1 (SDF-1)/CXCR4 signaling play key role in homing and mobilization of hematopoietic progenitor (HPC) and hematopoietic cancer clonogenic cells (HCC). High expression of VLA-4 is required for homing of HPC and HCC, whereas downregulation of these molecules is required ...

    journal_title:Leukemia

    pub_type: 杂志文章,评审

    doi:10.1038/sj.leu.2403173

    authors: Gazitt Y

    更新日期:2004-01-01 00:00:00

  • Hematopoietic differentiation of umbilical cord blood-derived very small embryonic/epiblast-like stem cells.

    abstract::A population of CD133(+)Lin(-)CD45(-) very small embryonic/epiblast-like stem cells (VSELs) has been purified by multiparameter sorting from umbilical cord blood (UCB). To speed up isolation of these cells, we employed anti-CD133-conjugated paramagnetic beads followed by staining with Aldefluor to detect aldehyde dehy...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2011.73

    authors: Ratajczak J,Zuba-Surma E,Klich I,Liu R,Wysoczynski M,Greco N,Kucia M,Laughlin MJ,Ratajczak MZ

    更新日期:2011-08-01 00:00:00

  • Importance of MEK-1/-2 signaling in monocytic and granulocytic differentiation of myeloid cell lines.

    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 ...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2402400

    authors: Miranda MB,McGuire TF,Johnson DE

    更新日期:2002-04-01 00:00:00

  • Immunoglobulin and T cell receptor gene rearrangement and expression in B cell acute lymphoblastic leukemia.

    abstract::Immunoglobulin and T cell receptor gene rearrangement and expression were investigated within B cell acute lymphoblastic leukemias (ALLs) that are thought to be representative of the early stages of normal human B cell development. Although the immunoglobulin heavy chain locus is rearranged in leukemic cells from all ...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Kinnon C,Katz F

    更新日期:1989-11-01 00:00:00

  • Myeloid differentiation antigens identify leukemic cell subpopulations with different cell cycle characteristics.

    abstract::In order to assess the proliferative capacity of leukemic subpopulations and to know whether it can be related to the stage of maturation, the expression of two surface antigens identifying distinct steps of leukocyte differentiation (CD15 and CD34) was studied by flow cytometry in correlation with DNA content in 16 c...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Campos L,Ffrench M,Guyotat D

    更新日期:1990-01-01 00:00:00

  • Molecular characterization of jumping translocations reveals spatial and temporal breakpoint heterogeneity.

    abstract::Jumping translocations (JT) are characterized by the relocalization of the same part of a donor to several recipient chromosomes. Although JT occasionally are constitutional, most are associated with hematologic malignancies. In such cases, JT usually arise during disease progression and are associated with poor progn...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2401108

    authors: Andreasson P,Höglund M,Jonson T,Békàssy A,Mitelman F,Johansson B

    更新日期:1998-09-01 00:00:00

  • The impact of differential binding of wild-type RARalpha, PML-, PLZF- and NPM-RARalpha fusion proteins towards transcriptional co-activator, RIP-140, on retinoic acid responses in acute promyelocytic leukemia.

    abstract::Retinoic acid receptor (RA) heterodimer (RAR/RXR) activities have been shown to be repressed by transcriptional co-repressor, SMRT/N-CoR, in the absence of the ligand while upon all-trans retionic acid (ATRA) treatment, SMRT/N-CoR is dissociated from RARalpha leading to gene expression by the recruitment of transcript...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2401643

    authors: So CW,Dong S,So CK,Cheng GX,Huang QH,Chen SJ,Chan LC

    更新日期:2000-01-01 00:00:00

  • Management of infective complications in patients with advanced hematologic malignancies in home care.

    abstract::A home care service has been implemented at our center with the aim of offering domiciliary assistance to patients with hematologic malignancies in advanced phase. We report our experience concerning the home management of these patients in the setting of infective complications. Of 151 patients in home care, 70 (46%)...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/sj.leu.2400851

    authors: Girmenia C,Moleti ML,Cartoni C,Cedrone M,De Gregoris C,De Sanctis V,Giovannini M,Latagliata R,Niscola P,Romani C,Rondinelli MB,Tosti S,Mandelli F

    更新日期:1997-11-01 00:00:00

  • Increased levels of interleukin-6 (IL-6) in serum and spontaneous in vitro production of IL-6 by lymph node mononuclear cells of patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD), and clinical effectiveness of cyclosporin A.

    abstract::Serum levels of cytokines and in vitro cytokine production by lymph node mononuclear cells (LNMC) were studied in four patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) or AILD-type T cell lymphoma. An increased level of serum interleukin-6 (IL-6) was detected on initial diagnosis in both of...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Yamamura M,Honda M,Yamada Y,Itoyama T,Sohda H,Yubashi T,Momita S,Kamihira S,Ohmoto Y,Tomonaga M

    更新日期:1996-09-01 00:00:00

  • Kinetics of chimerism during the early post-transplant period in pediatric patients with malignant and non-malignant hematologic disorders: implications for timely detection of engraftment, graft failure and rejection.

    abstract::The monitoring of chimerism by PCR has become a routine diagnostic approach in patients after allogeneic bone marrow or peripheral blood stem cell transplantation. Nevertheless, a temporal correlation between molecular and hematologic assessment of engraftment has not been clearly established. To address this issue, a...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:

    authors: Dubovsky J,Daxberger H,Fritsch G,Printz D,Peters C,Matthes S,Gadner H,Lion T,Muller-Bérat N

    更新日期:1999-12-01 00:00:00

  • Strong association of the HLA-DP6 supertype with childhood leukaemia is due to a single allele, DPB1*0601.

    abstract::We previously reported that susceptibility to childhood B cell precursor ALL (BCP ALL) is associated with HLA-DPB1 alleles having glutamic acid (E) rather than lysine (K) in the P4 antigenic peptide-binding pocket. Clustering approximately 90% of DPB1 alleles into DPB69E (DP2, 6, 8) and DPB69K (DP1, 3, 4) supertypes r...

    journal_title:Leukemia

    pub_type: 杂志文章

    doi:10.1038/leu.2008.374

    authors: Taylor GM,Hussain A,Verhage V,Thompson PD,Fergusson WD,Watkins G,Lightfoot T,Harrison CJ,Birch JM,UKCCS Investigators.

    更新日期:2009-05-01 00:00:00