• Disease
  • Sideroblastic
  • Sideroblastic Anemia
  • Mark D Fleming

    Prominent publications by Mark D Fleming

    KOL Index score: 13922

    Bone morphogenetic protein (BMP) signaling induces hepatic expression of the peptide hormone hepcidin. Hepcidin reduces serum iron levels by promoting degradation of the iron exporter ferroportin. A relative deficiency of hepcidin underlies the pathophysiology of many of the genetically distinct iron overload disorders, collectively termed hereditary hemochromatosis. Conversely, chronic inflammatory conditions and neoplastic diseases can induce high hepcidin levels, leading to impaired ...

    Also Ranks for: Bmp Type |  iron overload |  hepcidin expression |  alk2 alk3 |  mice mice
    KOL Index score: 13796

    Iron-refractory, iron-deficiency anemia (IRIDA) is a familial disorder characterized by iron deficiency anemia unresponsive to oral iron treatment but partially responsive to intravenous iron therapy. Previously, we showed that IRIDA patients harbor loss-of-function mutations in TMPRSS6, a type II transmembrane serine protease primarily expressed by the liver. Both humans and mice with TMPRSS6 mutations show inappropriately elevated levels of the iron-regulatory hormone hepcidin, ...

    Also Ranks for: Systemic Iron Homeostasis |  bmp smad |  mice tmprss6 |  hepcidin expression |  knockout rna
    KOL Index score: 12673

    The Belgrade (b) rat has an autosomal recessively inherited, microcytic, hypochromic anemia associated with abnormal reticulocyte iron uptake and gastrointestinal iron absorption. The b reticulocyte defect appears to be failure of iron transport out of endosomes within the transferrin cycle. Aspects of this phenotype are similar to those reported for the microcytic anemia (mk) mutation in the mouse. Recently, mk has been attributed to a missense mutation in the gene encoding the putative ...

    Also Ranks for: Iron Transport |  nramp2 protein |  mk mouse |  microcytic anemia |  transferrin cycle
    KOL Index score: 12387

    It has been suggested that a switch in chemokine receptor expression underlies Langerhans cell migration from skin to lymphoid tissue. Activated cells are thought to down-regulate CCR6, whose ligand macrophage inflammatory protein-3 alpha (MIP-3 alpha)/CCL20 is expressed in skin, and up-regulate CCR7, whose ligands are in lymphoid tissues. In Langerhans cell histiocytosis (LCH), pathologic Langerhans cells (LCs) accumulate in several tissues, including skin, bone, and lymphoid organs. We ...

    Also Ranks for: Langerhans Cell Histiocytosis |  chemokine receptors |  ccr6 ccr7 |  skin bone |  lymphoid tissues
    KOL Index score: 12297

    Patients with hematologic malignancies undergoing allogeneic stem cell transplantation (HSCT) commonly have an elevated serum ferritin prior to HSCT, which has been associated with increased mortality after transplantation. This has led to the suggestion that iron overload is common and deleterious in this patient population. However, the relationship between serum ferritin and parenchymal iron overload in such patients is unknown. We report a prospective study of 48 patients with acute ...

    Also Ranks for: Acute Leukemia |  iron overload |  cell transplantation |  serum ferritin |  myelodysplastic syndromes
    KOL Index score: 12173

    BACKGROUND: Sideroblastic anemias are heterogeneous congenital and acquired bone marrow disorders characterized by pathologic iron deposits in mitochondria of erythroid precursors. Among the congenital sideroblastic anemias (CSAs), the most common form is X-linked sideroblastic anemia, due to mutations in 5-aminolevulinate synthase (ALAS2). A novel autosomal recessive CSA, caused by mutations in the erythroid specific mitochondrial transporter SLC25A38, was recently defined. Other known ...

    Also Ranks for: Congenital Sideroblastic Anemia |  sideroblastic child child |  alas2 slc25a38 |  mitochondrial membrane |  common form
    KOL Index score: 11723

    KRAS is often mutated in human hematopoietic malignancies, including juvenile myelomonocytic leukemia (JMML) and T-cell lymphoblastic leukemia/lymphoma (TLL/L). However, the exact role and function of oncogenic KRAS mutations in the initiation and progression of JMML and TLL/L remain elusive. Here, we report the use of a mouse bone marrow transplantation model to study oncogenic Kras-induced leukemogenesis. We show that as the first genetic hit, oncogenic Kras mutations initiate both ...

    Also Ranks for: Oncogenic Kras |  stem cell |  myeloid progenitors |  solid tumors |  transformation neoplastic
    KOL Index score: 11251

    We describe the cloning of p63, a gene at chromosome 3q27-29 that bears strong homology to the tumor suppressor p53 and to the related gene, p73. p63 was detected in a variety of human and mouse tissues, including proliferating basal cells of epithelial layers in the epidermis, cervix, urothelium, and prostate. Unlike p53, the p63 gene encodes multiple isotypes with remarkably divergent abilities to transactivate p53 reporter genes and induce apoptosis. Importantly, the predominant p63 ...

    Also Ranks for: P53 Homolog |  tumor suppressor genes |  situ hybridization |  encodes multiple |  proteins mice
    KOL Index score: 11201

    Hereditary hemochromatosis, which is characterized by inappropriately low levels of hepcidin, increased dietary iron uptake, and systemic iron accumulation, has been associated with mutations in the HFE, transferrin receptor-2 (TfR2), and hemojuvelin (HJV) genes. However, it is still not clear whether these molecules intersect in vivo with bone morphogenetic protein 6 (BMP6)/mothers against decapentaplegic (SMAD) homolog signaling, the main pathway up-regulating hepcidin expression in ...

    Also Ranks for: Iron Phenotype |  morphogenetic protein |  bmp6 hjv |  hepcidin expression response |  deficient mice
    KOL Index score: 11083

    Proteins with iron-sulfur (Fe-S) clusters participate in multiple metabolic pathways throughout the cell. The mitochondrial ABC half-transporter Abcb7, which is mutated in X-linked sideroblastic anemia with ataxia in humans, is a functional ortholog of yeast Atm1p and is predicted to export a mitochondrially derived metabolite required for cytosolic Fe-S cluster assembly. Using an inducible Cre/loxP system to delete exons 9 and 10 of the Abcb7 gene, we examined the phenotype of mice ...

    Also Ranks for: Cytosolic Iron |  sulfur cluster |  binding cassette |  mitochondrial atp |  transporter abcb7
    KOL Index score: 11033

    A number of genetic mutations have been identified in human breast cancers, yet the specific combinations of mutations required in concert to form breast carcinoma cells remain unknown. One approach to identifying the genetic and biochemical alterations required for this process involves the transformation of primary human mammary epithelial cells (HMECs) to carcinoma cells through the introduction of specific genes. Here we show that introduction of three genes encoding the SV40 large-T ...

    Also Ranks for: Human Breast |  mammary epithelial |  oncogenic transformation |  cells tumors |  tumor formation
    KOL Index score: 10744

    Although the physiological role of tissue-specific translational control of gene expression in mammals has long been suspected on the basis of biochemical studies, direct evidence has been lacking. Here, we report on the targeted disruption of the gene encoding the heme-regulated eIF2alpha kinase (HRI) in mice. We establish that HRI, which is expressed predominantly in erythroid cells, regulates the synthesis of both alpha- and beta-globins in red blood cell (RBC) precursors by ...

    Also Ranks for: Erythroid Precursors |  translational regulation |  iron deficiency |  eif2α kinase |  cell survival
    KOL Index score: 10743

    Microcytic anemia (mk) mice and Belgrade (b) rats have severe iron deficiency anemia due to defects in intestinal iron transport and erythroid iron utilization. Both animal mutants carry the same missense mutation in Nramp2, the first mammalian iron transporter to be identified. This mutation, in which glycine 185 is changed to arginine (G185R), occurs within predicted transmembrane domain 4 of the protein. We have performed site-directed mutagenesis of murine Nramp2, focusing on amino ...

    Also Ranks for: Iron Transport |  g185r mutation |  cultured cloning |  transmembrane domain |  nramp2 function
    KOL Index score: 10620

    Oncogenic NRAS mutations are frequently identified in myeloid diseases involving monocyte lineage. However, its role in the genesis of these diseases remains elusive. We report a mouse bone marrow transplantation model harboring an oncogenic G12D mutation in the Nras locus. Approximately 95% of recipient mice develop a myeloproliferative disease resembling the myeloproliferative variant of chronic myelomonocytic leukemia (CMML), with a prolonged latency and acquisition of multiple ...

    Also Ranks for: Oncogenic Nras |  chronic myelomonocytic |  csf signaling |  murine model |  cmml cells


    Mark D Fleming: Influence Statistics

    Sample of concepts for which Mark D Fleming is among the top experts in the world.
    Concept World rank
    symptomatic adult anemia #1
    epp hri #1
    cell proliferation sirt3 #1
    murine mutants study #1
    csas context #1
    compensatory clonal #1
    bgh sinuses #1
    transgenic mutation hfe #1
    inherited forms mutations #1
    16 trf #1
    regular blood loss #1
    tfbound iron uptake #1
    flvcr1 exports heme #1
    molecules hfe #1
    loss hfe #1
    mutations publication anemia #1
    hscb female patient #1
    protein ndufb11 #1
    betathalassemia tmprss6 #1
    mrna severe #1
    alas2 gene study #1
    syncytiotrophoblast ferroportin #1
    amino acid arg216gln #1
    protein belgrade rat #1
    intracellular organelles metals #1
    antisense tmprss6 #1
    oral deferiprone improvement #1
    transport g185r #1
    flexedtail animals #1
    additively diminishes #1
    sec15 proteins #1
    antioxidant responsiveness #1
    tmprss6 decreases #1
    new ironloading disorders #1
    epp betathalassemia #1
    iron deficiency mutations #1
    mouse placentas mid #1
    ability molecular diagnosis #1
    structurefunction work steap4 #1
    nramp2 function #1
    sideroblastic animals #1
    abcb7 essential #1
    cybrd1 duodenal cytochrome #1
    mice alk3 #1
    alas alas2 #1
    longsought heme transporter #1
    uncommon diverse class #1
    hfe hfemediated induction #1
    hjv hfemediated induction #1
    erythrocyte ppix levels #1

    Key People For Sideroblastic Anemia

    Top KOLs in the world
    Sylvia S Bottomley
    sideroblastic anemia iron overload heme biosynthesis
    David F Bishop
    fabry disease uroporphyrinogen iii synthase acute intermittent porphyria
    Alison May
    sideroblastic anaemia prenatal diagnosis iron overload
    Mark D Fleming
    sideroblastic anemia iron deficiency myelodysplastic syndrome
    Philip D Cotter
    situ hybridization prenatal diagnosis human pair
    Dean R Campagna
    sideroblastic anemia gata2 mutations iron deficiency

    Mark D Fleming:Expert Impact

    Concepts for whichMark D Fleminghas direct influence:Sideroblastic anemia,  Iron deficiency,  Iron overload,  Myelodysplastic syndrome,  Iron transport,  Hepcidin expression,  Acute myeloid leukaemia,  Bone marrow.

    Mark D Fleming:KOL impact

    Concepts related to the work of other authors for whichfor which Mark D Fleming has influence:Cancer cells,  Iron metabolism,  Gene expression,  Pyruvate kinase,  Oxidative stress,  Ewing sarcoma,  Langerhans cell histiocytosis.



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    Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, United States of America | Department of Pathology, Boston Children’s Hospital, Harvard Medical School, Boston, MA; | Department of Pathology, Boston Children's Hosp