Marrow failure.

This chapter describes the clinical presentation and molecular basis of two inherited bone marrow failure syndromes, Fanconi anemia (FA), and Diamond-Blackfan anemia (DBA). It also provides an update on diagnostic and therapeutic approaches to bone marrow failure of all types (inherited and acquired) in pediatric patients. In Section I, Dr. Alan D'Andrea reviews the wide range of clinical manifestations of Fanconi anemia. Significant advances have been made in understanding the molecular pathogenesis of FA. On the basis of these advances, new diagnostic assays and treatment options are now available. In Section II, Dr. Niklas Dahl examines the clinical features and molecular pathogenesis of Diamond-Blackfan anemia. The possible links between the RPS19 gene (DBA gene) and the erythropoiesis defect are considered. In Section III, Drs. Eva Guinan and Akiko Shimamura provide an algorithm for the diagnostic evaluation and treatment of children with inherited or acquired aplastic anemia. Through the presentation of a case study of a pediatric patient with bone marrow failure, he provides an overview of the newest tests and treatment options.

[1]  E. Keohane.  Acquired Aplastic Anemia , 2004, American Society for Clinical Laboratory Science.

[2]  G. Gerrits,et al.  Transient erythroblastopenia of childhood , 1984, European Journal of Pediatrics.

[3]  S. Nand.  Blood: Principles and Practice of Hematology , 2003 .

[4]  Alan D. D'Andrea.  Fanconi anemia , 2003, Current Biology.

[5]  N. Dahl,et al.  Familial transient erythroblastopenia of childhood is associated with the chromosome 19q13.2 region but not caused by mutations in coding sequences of the ribosomal protein S19 (RPS19) gene , 2002, British journal of haematology.

[6]  D. Malkin,et al.  Clonal evolution in marrows of patients with Shwachman-Diamond syndrome: a prospective 5-year follow-up study. , 2002, Experimental Hematology.

[7]  Hans Joenje,et al.  Biallelic Inactivation of BRCA2 in Fanconi Anemia , 2002, Science.

[8]  S. Orkin,et al.  Transcriptional regulation of erythropoiesis: an affair involving multiple partners , 2002, Oncogene.

[9]  DAVID C. Christian.  Computer-assisted analysis of oral brush biopsies at an oral cancer screening program. , 2002, Journal of the American Dental Association.

[10]  M. Koury,et al.  New insights into erythropoiesis , 2002, Current opinion in hematology.

[11]  A. D’Andrea,et al.  Molecular Pathogenesis of Fanconi Anemia , 2002, International journal of hematology.

[12]  R. Kanaar,et al.  Brca2 (XRCC11) Deficiency Results in Radioresistant DNA Synthesis and a Higher Frequency of Spontaneous Deletions , 2002, Molecular and Cellular Biology.

[13]  D. Follmann,et al.  Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome. , 2001, Blood.

[14]  H. Nishiura,et al.  Identification of receptor-binding sites of monocyte chemotactic S19 ribosomal protein dimer. , 2001, The American journal of pathology.

[15]  A. Barrett,et al.  Oligoclonal T cell expansion in myelodysplastic syndrome: evidence for an autoimmune process. , 2001, Leukemia research.

[16]  F. Amalric,et al.  Fibroblast growth factor-2 interacts with free ribosomal protein S19. , 2001, Biochemical and biophysical research communications.

[17]  Richard J. Jones,et al.  Multilineage glycosylphosphatidylinositol anchor‐deficient haematopoiesis in untreated aplastic anaemia , 2001, British journal of haematology.

[18]  A. D’Andrea,et al.  Fanconi anemia and DNA repair. , 2001, Human molecular genetics.

[19]  A. D’Andrea,et al.  Functional analysis of patient-derived mutations in the Fanconi anemia gene, FANCG/XRCC9. , 2001, Experimental hematology.

[20]  E. Zackai,et al.  Bilateral microtia and cleft palate in cousins with Diamond-Blackfan anemia. , 2001, American journal of medical genetics.

[21]  Hans Joenje,et al.  The emerging genetic and molecular basis of Fanconi anaemia , 2001, Nature Reviews Genetics.

[22]  S. Batish,et al.  Evaluation of Growth and Hormonal Status in Patients Referred to the International Fanconi Anemia Registry , 2001, Pediatrics.

[23]  K. Devriendt,et al.  Identification of novel DKC1 mutations in patients with dyskeratosis congenita: implications for pathophysiology and diagnosis , 2001, Human Genetics.

[24]  M. Daly,et al.  Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease. , 2001, Blood.

[25]  R. Moses,et al.  Positional cloning of a novel Fanconi anemia gene, FANCD2. , 2001, Molecular cell.

[26]  S. Ganesan,et al.  Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. , 2001, Molecular cell.

[27]  L. D. Da Costa,et al.  Diamond-Blackfan Anemia , 2019, Clinical Disorders and Experimental Models of Erythropoietic Failure.

[28]  F. Locatelli,et al.  Stem cell transplantation from HLA-matched related donor for Fanconi's anaemia: a retrospective review of the multicentric Italian experience on behalf of AIEOP-GITMO. , 2001, British journal of haematology.

[29]  M. Ballmaier,et al.  c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia. , 2001, Blood.

[30]  C. Lewis,et al.  Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group. , 2000, Blood.

[31]  N. Alon,et al.  Isolation of a cDNA representing the Fanconi anemia complementation group E gene. , 2000, American journal of human genetics.

[32]  A. Yoshimi,et al.  Long‐term outcome of acquired aplastic anaemia in children: comparison between immunosuppressive therapy and bone marrow transplantation , 2000, British journal of haematology.

[33]  I. Dianzani,et al.  Diamond-Blackfan anemia: report of seven further mutations in the RPS19 gene and evidence of mutation heterogeneity in the Italian population. , 2000, Blood cells, molecules & diseases.

[34]  A. Weissman,et al.  RING Finger Proteins Mediators of Ubiquitin Ligase Activity , 2000, Cell.

[35]  J. Wagner,et al.  Haematopoietic cell transplantation in patients with Fanconi anaemia using alternate donors: results of a total body irradiation dose escalation trial , 2000, British journal of haematology.

[36]  T. Barbui,et al.  Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. European Group for Blood and Marrow Transplantation (EBMT) Working Party on Severe Aplastic Anemia and the Gruppo Italiano Tra , 2000, Blood.

[37]  F. Locatelli,et al.  Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLA-matched unrelated donors: a study on behalf of the European Group for Blood and Marrow Transplantation. , 2000, Blood.

[38]  M. Horowitz,et al.  Current status of allogeneic bone marrow transplantation in acquired aplastic anemia. , 2000, Seminars in hematology.

[39]  R. Brand,et al.  Treatment of acquired severe aplastic anemia: bone marrow transplantation compared with immunosuppressive therapy--The European Group for Blood and Marrow Transplantation experience. , 2000, Seminars in hematology.

[40]  N. Frickhofen,et al.  Immunosuppressive treatment of aplastic anemia with antithymocyte globulin and cyclosporine. , 2000, Seminars in hematology.

[41]  D. Margolis,et al.  Alternative-donor hematopoietic stem-cell transplantation for severe aplastic anemia. , 2000, Seminars in hematology.

[42]  F. Sigaux,et al.  Aplastic anemia and paroxysmal nocturnal hemoglobinuria: a follow-up study of the glycosylphosphatidylinositol-anchored proteins defect. , 2000, The hematology journal : the official journal of the European Haematology Association.

[43]  I. Dianzani,et al.  Mutations in ribosomal protein S19 gene and diamond blackfan anemia: wide variations in phenotypic expression. , 1999, Blood.

[44]  K. Collins,et al.  A telomerase component is defective in the human disease dyskeratosis congenita , 1999, Nature.

[45]  N. Young,et al.  Engraftment of hematopoietic progenitor cells transduced with the Fanconi anemia group C gene (FANCC). , 1999, Human gene therapy.

[46]  H. Nishiura,et al.  Determination of the cross-linked residues in homo-dimerization of S19 ribosomal protein concomitant with exhibition of monocyte chemotactic activity. , 1999, Laboratory investigation; a journal of technical methods and pathology.

[47]  C. Mathew,et al.  Spontaneous functional correction of homozygous Fanconi anaemia alleles reveals novel mechanistic basis for reverse mosaicism , 1999, Nature Genetics.

[48]  J. V. Stone,et al.  Long-Term Survival and Late Deaths after Allogeneic Bone Marrow Transplantation , 1999 .

[49]  A. Kanamaru,et al.  Detection of GPI‐anchored protein‐deficient cells in patients with aplastic anaemia and evidence for clonal expansion during the clinical course , 1999, British journal of haematology.

[50]  Peter Gustavsson,et al.  The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia , 1999, Nature Genetics.

[51]  I. Dianzani,et al.  IDENTIFICATION OF MICRODELETIONS SPANNING THE DIAMOND-BLACKFAN ANEMIA (DBA) LOCUS ON 19Q13 AND EVIDENCE FOR GENETIC HETEROGENEITY , 1998, Pediatric Research.

[52]  B. Alter.  Bone marrow failure syndromes. , 1991, Clinics in laboratory medicine.

[53]  J. V. Stone,et al.  Long-term survival and late deaths after allogeneic bone marrow transplantation. Late Effects Working Committee of the International Bone Marrow Transplant Registry. , 1999, The New England journal of medicine.

[54]  D. Bowers,et al.  Truncating ribosomal protein S19 mutations and variable clinical expression in Diamond-Blackfan anemia , 1999, Human Genetics.

[55]  M. Freedman,et al.  Shwachman-Diamond syndrome: An inherited preleukemic bone marrow failure disorder with aberrant hematopoietic progenitors and faulty marrow microenvironment. , 1999, Blood.

[56]  M. Sagmeister,et al.  A restrictive platelet transfusion policy allowing long-term support of outpatients with severe aplastic anemia. , 1999, Blood.

[57]  A. Barrett,et al.  Haematological response of patients with myelodysplastic syndrome to antithymocyte globulin is associated with a loss of lymphocyte‐mediated inhibition of CFU‐GM and alterations in T‐cell receptor Vβ profiles , 1998, British journal of haematology.

[58]  F. Couch,et al.  Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. , 1998, Molecular cell.

[59]  E. Guinan,et al.  Subtyping Analysis of Fanconi Anemia by Immunoblotting and Retroviral Gene Transfer , 1998, Molecular medicine.

[60]  H. Deeg,et al.  Long-term outcome after marrow transplantation for severe aplastic anemia. , 1998, Blood.

[61]  S. Klauck,et al.  X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions , 1998, Nature Genetics.

[62]  B. Ponder,et al.  Involvement of Brca2 in DNA repair. , 1998, Molecular cell.

[63]  A. Gratwohl,et al.  Repeated treatment with horse antilymphocyte globulin for severe aplastic anaemia , 1998, British journal of haematology.

[64]  A. Ashworth,et al.  Tumorigenesis and a DNA repair defect in mice with a truncating Brca2 mutation , 1997, Nature Genetics.

[65]  D. Näf,et al.  The Fanconi anaemia proteins, FAA and FAC interact to form a nuclear complex , 1997, Nature Genetics.

[66]  M. Buchwald,et al.  Evidence for at least eight Fanconi anemia genes. , 1997, American journal of human genetics.

[67]  N. Young,et al.  Retroviral mediated gene transfer of the Fanconi anemia complementation group C gene to hematopoietic progenitors of group C patients. , 1997, Human gene therapy.

[68]  N. Dahl,et al.  Diamond-Blackfan anaemia in a girl with a de novo balanced reciprocal X;19 translocation. , 1997, Journal of medical genetics.

[69]  P. Nilsson,et al.  Diamond-Blackfan anaemia: genetic homogeneity for a gene on chromosome 19q13 restricted to 1.8 Mb , 1997, Nature Genetics.

[70]  J. Klein,et al.  Bone marrow transplantation for severe aplastic anemia: has outcome improved? , 1997, Blood.

[71]  A D Auerbach,et al.  Phenotypic consequences of mutations in the Fanconi anemia FAC gene: an International Fanconi Anemia Registry study. , 1997, Blood.

[72]  C. Mathew,et al.  Somatic Mosaicism in Fanconi Anemia: Molecular Basis and Clinical Significance , 1997, European journal of human genetics : EJHG.

[73]  P. Giampietro,et al.  Diagnosis of Fanconi anemia in patients without congenital malformations: an international Fanconi Anemia Registry Study. , 1997, American journal of medical genetics.

[74]  R. Moses,et al.  Complementation group assignments in fanconi anemia fibroblast cell lines from North America , 1997, Somatic cell and molecular genetics.

[75]  Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. , 1997, The New England journal of medicine.

[76]  C. Mathew,et al.  Positional cloning of the Fanconi anaemia group A gene , 1996, Nature Genetics.

[77]  B. Alter.  Fanconi's anemia and malignancies , 1996, American journal of hematology.

[78]  C. McGuckin,et al.  Diamond‐Blackfan anaemia in the U.K.: analysis of 80 cases from a 20‐year birth cohort , 1996, British journal of haematology.

[79]  J. Wagner,et al.  Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease. , 1996, Blood.

[80]  I. Wool.  Extraribosomal functions of ribosomal proteins. , 1996, Trends in biochemical sciences.

[81]  I. Dianzani,et al.  Mutations in the erythropoietin receptor gene are not a common cause of Diamond-Blackfan anemia. , 1996, Blood.

[82]  E. Guinan,et al.  Diamond-Blackfan anemia. Natural history and sequelae of treatment. , 1996, Medicine.

[83]  I. Wool,et al.  24 Mammalian Ribosomes: The Structure and the Evolution of the Proteins , 1996 .

[84]  O. Meyuhas,et al.  13 Translational Control of Ribosomal Protein mRNAs in Eukaryotes , 1996 .

[85]  J. Wagner,et al.  Unrelated donor bone marrow transplantation for Fanconi anemia. , 1996, Bone marrow transplantation.

[86]  A. Auerbach,et al.  Carrier frequency of the IVS4 + 4 A-->T mutation of the Fanconi anemia gene FAC in the Ashkenazi Jewish population. , 1995, Blood.

[87]  M. Buchwald.  Complementation groups: one or more per gene? , 1995, Nature Genetics.

[88]  J. Klein,et al.  Bone marrow transplantation for Fanconi anemia. , 1995, Blood.

[89]  C. McGuckin,et al.  Diamond‐Blackfan anaemia: three patterns of in vitro response to haemopoietic growth factors , 1995, British journal of haematology.

[90]  M. Arnaout,et al.  Red Cell Aplasia Resembling Diamond‐Blackfan Anemia in Seven Children in a Family , 1994, The American journal of pediatric hematology/oncology.

[91]  F. Laski,et al.  string of pearls encodes Drosophila ribosomal protein S2, has Minute-like characteristics, and is required during oogenesis. , 1994, Genetics.

[92]  E. Guinan,et al.  Evaluation of granulocyte-macrophage colony-stimulating factor for treatment of pancytopenia in children with fanconi anemia. , 1994, The Journal of pediatrics.

[93]  A. Auerbach,et al.  Bone marrow transplantation in Fanconi anemia using matched sibling donors. , 1994, Blood.

[94]  B. Alter.  FANCONI'S ANAEMIA AND ITS VARIABILITY , 1994, British journal of haematology.

[95]  A. Tichelli,et al.  Malignant tumors occurring after treatment of aplastic anemia. European Bone Marrow Transplantation-Severe Aplastic Anaemia Working Party. , 1993, The New England journal of medicine.

[96]  M. Wilcox,et al.  A Minute encoding a ribosomal protein enhances wing morphogenesis mutants , 1993, Mechanisms of Development.

[97]  P. Ljungman,et al.  Relapse of aplastic anaemia after immunosuppressive treatment: a report from the European Bone Marrow Transplantation Group SAA Working Party , 1993, British journal of haematology.

[98]  S. Feig,et al.  Clinical Disorders and Experimental Models of Erythropoietic Failure , 1993 .

[99]  A. Auerbach.  Fanconi anemia diagnosis and the diepoxybutane (DEB) test. , 1993, Experimental hematology.

[100]  P. Giampietro,et al.  The need for more accurate and timely diagnosis in Fanconi anemia: a report from the International Fanconi Anemia Registry. , 1993, Pediatrics.

[101]  R. Gibson,et al.  A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews , 1993, Nature Genetics.

[102]  P. Bryant,et al.  Drosophila homolog of the human S6 ribosomal protein is required for tumor suppression in the hematopoietic system. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[103]  B. Alter,et al.  Dyskeratosis Congenita: Clinical and Genetic Heterogeneity Report of a New Case and Review of the Literature , 1992, The American journal of pediatric hematology/oncology.

[104]  W. R. Shannon,et al.  Cloning of cDNAs for Fanconi's anaemia by functional complementation , 1992, Nature.

[105]  A. Gratwohl,et al.  Morphology in patients with severe aplastic anemia treated with antilymphocyte globulin. , 1992, Blood.

[106]  G. Zauli,et al.  In vitro growth and regulation of bone marrow enriched CD34+ hematopoietic progenitors in Diamond-Blackfan anemia. , 1991, Blood.

[107]  M. Freedman,et al.  Fanconi's anaemia and pregnancy , 1991, British journal of haematology.

[108]  J. Carey,et al.  Congenital hypoplastic (Diamond-Blackfan) anemia in seven members of one kindred. , 1990, American journal of medical genetics.

[109]  M. Horowitz,et al.  Current status of allogeneic bone marrow transplantation. , 1990, Clinical transplants.

[110]  J. Lipton,et al.  An intrinsic progenitor defect in Diamond‐Blackfan anaemia , 1989, British journal of haematology.

[111]  D. Halperin,et al.  Diamond-blackfan anemia: etiology, pathophysiology, and treatment. , 1989, The American journal of pediatric hematology/oncology.

[112]  B. Glader,et al.  Elevated red cell adenosine deaminase activity: a marker of disordered erythropoiesis in Diamond‐Blackfan anaemia and other haematologic diseases , 1988, British journal of haematology.

[113]  J. Fay,et al.  A multicenter trial of antithymocyte globulin in aplastic anemia and related diseases. , 1988, Blood.

[114]  R. Storb,et al.  Clonal cytogenetic abnormalities in patients with otherwise typical aplastic anemia. , 1987, Experimental hematology.

[115]  F. Gardner,et al.  Improved classification of anemias by MCV and RDW. , 1983, American journal of clinical pathology.

[116]  B. Alter.  Childhood red cell aplasia , 1980 .

[117]  R. Storb,et al.  Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality. , 1976, Blood.

[118]  W. Wang,et al.  Congenital hypoplastic anemia. , 1976, Advances in pediatrics.