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6 - Inherited and acquired bone marrow failure syndromes associated with multiple cytopenias

from Section 1 - General and non-neoplastic hematopathology

Published online by Cambridge University Press:  03 May 2011

By
Sa A. Wang  and
Victor Zota
Edited by
Maria A. Proytcheva
Sa A. Wang
Affiliation:
University of Texas M.D. Anderson Cancer Center
Victor Zota
Affiliation:
Novartis Institutes for BioMedical Research, Inc.
Maria A. Proytcheva
Affiliation:
Northwestern University Medical School, Illinois
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Summary

Overview

Bone marrow failure syndrome consists of a group of rare diseases with the defining features of ineffective/defective hematopoiesis by the bone marrow and resultant peripheral cytopenia [1, 2]. Bone marrow failure can be attributed to a variety of mechanisms, such as loss of pluripotent hematopoietic stem cells; bone marrow replacement by metastatic carcinoma, lymphoma, leukemia or fibrosis; nutritional/metabolic disorder leading to maturation arrest or clonal hematopoietic stem neoplasm such as myelodysplastic syndromes. Aplastic anemia is the paradigm of the human bone marrow failure syndrome, characterized by peripheral cytopenia and a hypocellular marrow [1, 3, 4]. Injury to or loss of pluripotent hematopoietic stem cells, in the absence of an infiltrative disease of the bone marrow, is the major pathophysiologic characteristic of the disease [3, 4]. Aplastic anemia can result from either inherited or acquired causes. This chapter will discuss the bone marrow failure syndromes, both inherited and acquired, that are associated with multiple cytopenias.

Inherited bone marrow failure syndromes

The inherited bone marrow failure syndromes in children comprise a group of rare congenital disorders in which the bone marrow is unable to produce blood cells effectively resulting in unilineage or multilineage cytopenia (Table 6.1). These syndromes may present with or without physical anomalies [5]. Patients with inherited bone marrow failure syndromes are at risk for severe cytopenia, development of marrow cytogenetic abnormalities, myelodysplastic syndromes (MDS), and other malignancies [6].

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Diagnostic Pediatric Hematopathology , pp. 90 - 103
Publisher: Cambridge University Press
Print publication year: 2011

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References

Young, N.S., Acquired aplastic anemia. Annals of Internal Medicine, 2002. 136(7): 534–546.CrossRefGoogle ScholarPubMed
Brodsky, R.A. and Jones, R.J., Aplastic anaemia. Lancet, 2005. 365(9471): p. 1647–56.PubMed
Young, N.S. and Maciejewski, J., The pathophysiology of acquired aplastic anemia. The New England journal of medicine, 1997. 336(19): p. 1365–72.PubMed
Young, N.S., Calado, R.T., and Scheinberg, P., Current concepts in the pathophysiology and treatment of aplastic anemia. Blood, 2006. 108(8): p. 2509–19.PubMed
Alter, B., Inherited bone marrow failure syndromes. In Nathan DG, Orkin SH, Look AT, Ginsburg D Nathan and Oski's Hematology of Infancy and Childhood 6th edn., ed. O.S. Nathan, DG, Look, AT, Ginsburg, D. 2003, Philadelphia, PA: WB Saunders. 280–365.Google Scholar
Steele, J.M., et al., Disease progression in recently diagnosed patients with inherited marrow failure syndromes: a Canadian Inherited Marrow Failure Registry (CIMFR) report. Pediatric blood & cancer, 2006. 47(7): p. 918–25.PubMed
Bagby, G.L., JM Sloand, EM Schiffer, CA Marrow failure., in Hematology 2004, Am Soc Hematol Educ Program. p. 318–36.Google ScholarPubMed
Lieberman, L. and Dror, Y., Advances in understanding the genetic basis for bone-marrow failure. Current opinion in pediatrics, 2006. 18(1): p. 15–21.PubMed
Huck, K., et al., Delayed diagnosis and complications of Fanconi anaemia at advanced age – a paradigm. British journal of haematology, 2006. 133(2): p. 188–97.
Alter, B., Bone marrow failure: a child is not just a small adult (but an adult can have a childhood disease). 2005, Am Soc Hematol Educ Program: Hematology. p. 96–103.Google Scholar
D'Andrea, A.D., Susceptibility pathways in Fanconi's anemia and breast cancer. N Engl J Med. 362(20): 2010. p. 1909–19.CrossRefGoogle ScholarPubMed
Davies, A.A., et al., Role of BRCA2 in control of the RAD51 recombination and DNA repair protein. Molecular cell, 2001. 7(2): p. 273–82.PubMed
Godthelp, B.C., et al., Impaired DNA damage-induced nuclear Rad51 foci formation uniquely characterizes Fanconi anemia group D1. Oncogene, 2002. 21(32): p. 5002–5.PubMed
Faivre, L., et al., Association of complementation group and mutation type with clinical outcome in Fanconi anemia. European Fanconi Anemia Research Group. Blood, 2000. 96(13): p. 4064–70.PubMed
Meetei, A.R., et al., A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nature genetics, 2005. 37(9): p. 958–63.PubMed
Taniguchi, T. and D'Andrea, A.D., Molecular pathogenesis of Fanconi anemia: recent progress. Blood, 2006. 107(11): p. 4223–33.PubMed
Tamary, H. and Alter, B.P., Current diagnosis of inherited bone marrow failure syndromes. Pediatric hematology and oncology, 2007. 24(2): p. 87–99.PubMed
Xia, F., et al., Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining. Proceedings of the National Academy of Sciences of the United States of America, 2001. 98(15): p. 8644–9.PubMed
Gowen, L.C., et al., BRCA1 required for transcription-coupled repair of oxidative DNA damage. Science 1998. 281(5379): p. 1009–12.PubMed
Shimamura, A. and D'Andrea, A.D., Subtyping of Fanconi anemia patients: implications for clinical management. Blood, 2003. 102(9): p. 3459.PubMed
Kutler, D.I., et al., A 20-year perspective on the International Fanconi Anemia Registry (IFAR). Blood, 2003. 101(4): p. 1249–56.
Butturini, A., et al., Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study. Blood, 1994. 84(5): p. 1650–5.PubMed
Cassinat, B., et al., Constitutive elevation of serum alpha-fetoprotein in Fanconi anemia. Blood, 2000. 96(3): p. 859–63.PubMed
Giampietro, P.F., et al., The need for more accurate and timely diagnosis in Fanconi anemia: a report from the International Fanconi Anemia Registry. Pediatrics, 1993. 91(6): p. 1116–20.PubMed
Stetler-Stevenson, M., et al., Diagnostic utility of flow cytometric immunophenotyping in myelodysplastic syndrome. Blood, 2001. 98(4): p. 979–87.PubMed
Fabio, T., et al., Cell cycle analysis in the diagnosis of Fanconi's anemia. Haematologica, 2000. 85(4): p. 431–2.
Bechtold, A., et al., Prenatal exclusion/confirmation of Fanconi anemia via flow cytometry: a pilot study. Fetal diagnosis and therapy, 2006. 21(1): p. 118–24.PubMed
Auerbach, A.D., Fanconi anemia diagnosis and the diepoxybutane (DEB) test. Experimental hematology, 1993. 21(6): p. 731–3.PubMed
Digweed, M. and Sperling, K., Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks. DNA repair, 2004. 3(8–9): p. 1207–17.PubMed
Maarek, O., et al., Faconi anemia and bone marrow clonal chromosome abnormalities. Leukemia, 1996. 10(11): p. 1700–4.PubMed
Tonnies, H., et al., Clonal chromosomal aberrations in bone marrow cells of Fanconi anemia patients: gains of the chromosomal segment 3q26q29 as an adverse risk factor. Blood, 2003. 101(10): p. 3872–4.PubMed
Alter, B.P., Leukemia and preleukemia in Fanconi's anemia. Cancer genetics and cytogenetics, 1992. 58(2): p. 206–8; discussion 209.PubMed
Alter, B.P., Fanconi's anemia and malignancies. American journal of hematology, 1996. 53(2): p. 99–110.PubMed
Guardiola, P., 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. Blood, 2000. 95(2): p. 422–9.
Zinsser, F., Atropha cutis reticularis cum pigmentatione, dystrophia ungiumet leukoplakia oris. Ikonogr Dermatol 1906. 5 p. 219–223.
Engman, M.F., A unique case of reticular pigmentation of the skin with atrophy. Archives of Dermatology and Syphiligraphie., 1926. 13 p. 685–687.
Cole, H.N., Rauschkolb, J.C., Toomey, J, Dyskeratosis congenita with pigmentation, dystrophia unguis and leukokeratosis oris. Archives of Dermatology and Syphiligraphie., 1930. 21 p. 71–95.
Dokal, I., Dyskeratosis congenita: an inherited bone marrow failure syndrome. British journal of haematology, 1996. 92(4): p. 775–9.
Sirinavin, C. and Trowbridge, A.A., Dyskeratosis congenita: clinical features and genetic aspects. Report of a family and review of the literature. Journal of medical genetics, 1975. 12(4): p. 339–54.PubMed
Drachtman, R.A. and Alter, B.P., Dyskeratosis congenita. Dermatologic clinics, 1995. 13(1): p. 33–9.PubMed
Knight, S., et al., Dyskeratosis Congenita (DC) Registry: identification of new features of DC. British journal of haematology, 1998. 103(4): p. 990–6.PubMed
Alter, B., Inherited Bone Marrow Failure Syndromes. Nathan and Oski's Hematology of Infancy and Childhood, ed. D. Nathan, Orkin, SH, Ginsburg, D, Look, AT. 2003, Philadelphia W. B. Saunders. 280.Google Scholar
Heiss, N.S., et al., X-linked dyskeratosis congenita is caused by mutations in a highly conserved gene with putative nucleolar functions. Nature genetics, 1998. 19(1): p. 32–8.
Knight, S.W., et al., X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene. American journal of human genetics, 1999. 65(1): p. 50–8.PubMed
Heiss, N.S., et al., Dyskerin localizes to the nucleolus and its mislocalization is unlikely to play a role in the pathogenesis of dyskeratosis congenita. Human molecular genetics, 1999. 8(13): p. 2515–24.PubMed
Youssoufian, H., V. Gharibyan, and M. Qatanani, Analysis of epitope-tagged forms of the dyskeratosis congenital protein (dyskerin): identification of a nuclear localization signal. Blood cells, molecules & diseases, 1999. 25(5–6): p. 305–9.PubMed
Aisner, D.L., W.E. Wright, and J.W. Shay, Telomerase regulation: not just flipping the switch. Current opinion in genetics & development, 2002. 12(1): p. 80–5.PubMed
Blackburn, E.H., Telomeres and telomerase: their mechanisms of action and the effects of altering their functions. FEBS letters, 2005. 579(4): p. 859–62.PubMed
Shay, J.W. and Wright, W.E., Senescence and immortalization: role of telomeres and telomerase. Carcinogenesis, 2005. 26(5): p. 867–74.PubMed
Mitchell, J.R., E. Wood, and K. Collins, A telomerase component is defective in the human disease dyskeratosis congenita. Nature, 1999. 402(6761): p. 551–5.PubMed
Vulliamy, T.J., et al., Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation. Blood, 2006. 107(7): p. 2680–5.PubMed
Vulliamy, T., et al., The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature, 2001. 413(6854): p. 432–5.PubMed
Armanios, M., et al., Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. Proceedings of the National Academy of Sciences of the United States of America, 2005. 102(44): p. 15960–4.PubMed
Vulliamy, T., et al., Disease anticipation is associated with progressive telomere shortening in families with dyskeratosis congenita due to mutations in TERC. Nature genetics, 2004. 36(5): p. 447–9.PubMed
Dokal, I., Dyskeratosis congenita in all its forms. British journal of haematology, 2000. 110(4): p. 768–79.PubMed
Dokal, I., Dyskeratosis congenita: recent advances and future directions. Journal of pediatric hematology/oncology, 1999. 21(5): p. 344–50.PubMed
Aalfs, C.M., et al., The Hoyeraal-Hreidarsson syndrome: the fourth case of a separate entity with prenatal growth retardation, progressive pancytopenia and cerebellar hypoplasia. European journal of pediatrics, 1995. 154(4): p. 304–8.PubMed
Knudson, M., et al., Association of immune abnormalities with telomere shortening in autosomal-dominant dyskeratosis congenita. Blood, 2005. 105(2): p. 682–8.PubMed
Bagby, G.C., et al., Marrow failure. Hematology / the Education Program of the American Society of Hematology. American Society of Hematology, 2004: p. 318–36.Google ScholarPubMed
Friedland, M., et al., Dyskeratosis congenita with hypoplastic anemia: a stem cell defect. American journal of hematology, 1985. 20(1): p. 85–7.PubMed
Marsh, J.C., et al., “Stem cell” origin of the hematopoietic defect in dyskeratosis congenita. Blood, 1992. 79(12): p. 3138–44.PubMed
Shwachman, H., et al., The Syndrome of Pancreatic Insufficiency and Bone Marrow Dysfunction. The Journal of pediatrics, 1964. 65: p. 645–63.PubMed
Aggett, P.J., et al., Shwachman's syndrome. A review of 21 cases. Archives of disease in childhood, 1980. 55(5): p. 331–47.PubMed
Mack, D.R., et al., Shwachman syndrome: exocrine pancreatic dysfunction and variable phenotypic expression. Gastroenterology, 1996. 111(6): p. 1593–602.PubMed
Ginzberg, H., et al., Shwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar. The Journal of pediatrics, 1999. 135(1): p. 81–8.
Dror, Y., et al., Immune function in patients with Shwachman-Diamond syndrome. British journal of haematology, 2001. 114(3): p. 712–7.PubMed
Hudson, E. and Aldor, T., Pancreatic insufficiency and neutropenia with associated immunoglobulin deficit. Archives of internal medicine, 1970. 125(2): p. 314–6.PubMed
Maki, M., et al., Hepatic dysfunction and dysgammaglobulinaemia in Shwachman-Diamond syndrome. Archives of disease in childhood, 1978. 53(8): p. 693–4.PubMed
Kornfeld, S.J., et al., Shwachman-Diamond syndrome associated with hypogammaglobulinemia and growth hormone deficiency. The Journal of allergy and clinical immunology, 1995. 96(2): p. 247–50.PubMed
Aggett, P.J., et al., An inherited defect of neutrophil mobility in Shwachman syndrome. The Journal of pediatrics, 1979. 94(3): p. 391–4.PubMed
Goobie, S., et al., Shwachman-Diamond syndrome with exocrine pancreatic dysfunction and bone marrow failure maps to the centromeric region of chromosome 7. American journal of human genetics, 2001. 68(4): p. 1048–54.PubMed
Alter, B., Inherited Bone Marrow Failure Syndromes. Nathan and Oski's Hematology of Infancy and Childhood, ed. D. Nathan, Orkin, SH, Ginsburg, D, Look, AT. 2003, Philadelphia: W.B. Saunders. p. 280.Google Scholar
Rothbaum, R.J., D.A. Williams, and C.C. Daugherty, Unusual surface distribution of concanavalin A reflects a cytoskeletal defect in neutrophils in Shwachman's syndrome. Lancet, 1982. 2(8302): p. 800–1.PubMed
Woloszynek, J.R., et al., Mutations of the SBDS gene are present in most patients with Shwachman-Diamond syndrome. Blood, 2004. 104(12): p. 3588–90.PubMed
Boocock, G.R., et al., Mutations in SBDS are associated with Shwachman-Diamond syndrome. Nature genetics, 2003. 33(1): p. 97–101.PubMed
Austin, K.M., R.J. Leary, and A. Shimamura, The Shwachman-Diamond SBDS protein localizes to the nucleolus. Blood, 2005. 106(4): p. 1253–8.PubMed
Boocock, G.R., M.R. Marit, and J.M. Rommens, Phylogeny, sequence conservation, and functional complementation of the SBDS protein family. Genomics, 2006. 87(6): p. 758–71.PubMed
Hall, G.W., P. Dale, and J.A. Dodge, Shwachman-Diamond syndrome: UK perspective. Archives of disease in childhood, 2006. 91(6): p. 521–4.PubMed
Dror, Y. and Freedman, M.H., Shwachman-Diamond syndrome: An inherited preleukemic bone marrow failure disorder with aberrant hematopoietic progenitors and faulty marrow microenvironment. Blood, 1999. 94(9): p. 3048–54.PubMed
Smith, O.P., et al., Haematological abnormalities in Shwachman-Diamond syndrome. British journal of haematology, 1996. 94(2): p. 279–84.PubMed
Woods, W.G., et al., The occurrence of leukemia in patients with the Shwachman syndrome. The Journal of pediatrics, 1981. 99(3): p. 425–8.PubMed
Dror, Y., Shwachman-Diamond syndrome. Pediatric blood & cancer, 2005. 45(7): p. 892–901.PubMed
Davies, S.M., et al., Unrelated donor bone marrow transplantation for children and adolescents with aplastic anaemia or myelodysplasia. British journal of haematology, 1997. 96(4): p. 749–56.PubMed
Freedman, M.H., et al., Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy. Blood, 2000. 96(2): p. 429–36.PubMed
Hasle, H., et al., A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia, 2003. 17(2): p. 277–82.PubMed
Dokal, I., et al., Adult onset of acute myeloid leukaemia (M6) in patients with Shwachman-Diamond syndrome. British journal of haematology, 1997. 99(1): p. 171–3.PubMed
Keller, P., et al., Bone marrow failure in Shwachman-Diamond syndrome does not select for clonal haematopoiesis of the paroxysmal nocturnal haemoglobinuria phenotype. British journal of haematology, 2002. 119(3): p. 830–2.
Mertens, F., B. Johansson, and F. Mitelman, Isochromosomes in neoplasia. Genes, chromosomes & cancer, 1994. 10(4): p. 221–30.PubMed
Dror, Y., et al., Clonal evolution in marrows of patients with Shwachman-Diamond syndrome: a prospective 5-year follow-up study. Experimental hematology, 2002. 30(7): p. 659–69.PubMed
Smith, A., et al., Intermittent 20q- and consistent i(7q) in a patient with Shwachman-Diamond syndrome. Pediatric hematology and oncology, 2002. 19(7): p. 525–8.
Pearson, H.A., et al., A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction. The Journal of pediatrics, 1979. 95(6): p. 976–84.PubMed
Fleming, M.D., The genetics of inherited sideroblastic anemias. Seminars in hematology, 2002. 39(4): p. 270–81.PubMed
Dubowitz, V., Familial Low Birthweight Dwarfism with an Unusual Facies and a Skin Eruption. Journal of medical genetics, 1965. 42: p. 12–7.
Berthold, F., W. Fuhrmann, and F. Lampert, Fatal aplastic anaemia in a child with features of Dubowitz syndrome. European journal of pediatrics, 1987. 146(6): p. 605–7.
Walters, T.R. and Desposito, F., Aplastic anemia in Dubowitz syndrome. The Journal of pediatrics, 1985. 106(4): p. 622–3.PubMed
Resnick, I.B., et al., Nijmegen breakage syndrome: clinical characteristics and mutation analysis in eight unrelated Russian families. The Journal of pediatrics, 2002. 140(3): p. 355–61.PubMed
Harper, R.G., E. Orti, and R.K. Baker, Bird-beaded dwarfs (Seckel's syndrome). A familial pattern of developmental, dental, skeletal, genital, and central nervous system anomalies. J Pediatr, 1967. 70(5): p. 799–804.PubMed
Dohlsten, M., et al., Immunological abnormalities in a child with constitutional aplastic anemia. Pediatric hematology and oncology, 1986. 3(1): p. 89–96.
Nathan DG, , Hematology of Infancy and Childhood. 2009, Philadelphia, PA: WB Saunders, Inc.Google Scholar
Young, N.S., et al., The relationship of aplastic anemia and PNH. International journal of hematology, 2002. 76 Suppl 2: p. 168–72.PubMed
Young, N., Drugs and chemicals., in Aplastic Anemia: Acquired and Inherited., A.B. Young, NS, Editor. 1994, WB Saunders: Philadelphia. p. 100–32.Google Scholar
Fuhrer, M., et al., Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival. Blood, 2005. 106(6): p. 2102–4.PubMed
Shimamura, A., Guinan, EA., Acquired aplastic anemia., in Hematology of Infancy and Childhood, Nathan, D., Orkin, SH Editor. 2003, WB Saunders: Philadelphia. p. 256.Google Scholar
Ly, H., et al., Functional characterization of telomerase RNA variants found in patients with hematologic disorders. Blood, 2005. 105(6): p. 2332–9.PubMed
Yamaguchi, H., et al., Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. The New England journal of medicine, 2005. 352(14): p. 1413–24.PubMed
Orazi, A., et al., Hypoplastic myelodysplastic syndromes can be distinguished from acquired aplastic anemia by CD34 and PCNA immunostaining of bone marrow biopsy specimens. American journal of clinical pathology, 1997. 107(3): p. 268–74.PubMed
Maciejewski, J.P., et al., Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia. Blood, 2002. 99(9): p. 3129–35.PubMed
Nakao, S., C. Sugimori, and H. Yamazaki, Clinical significance of a small population of paroxysmal nocturnal hemoglobinuria-type cells in the management of bone marrow failure. International journal of hematology, 2006. 84(2): p. 118–22.PubMed
Sugimori, C., et al., Minor population of CD55-CD59- blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia. Blood, 2006. 107(4): p. 1308–14.PubMed
Shichishima, T. and Noji, H., A new aspect of the molecular pathogenesis of paroxysmal nocturnal hemoglobinuria. Hematology (Amsterdam, Netherlands), 2002. 7(4): p. 211–27.PubMed
Young, N.S., Paroxysmal nocturnal hemoglobinuria: current issues in pathophysiology and treatment. Current hematology reports, 2005. 4(2): p. 103–9.PubMed
Fuhrer, M., et al., Relapse and clonal disease in children with aplastic anemia (AA) after immunosuppressive therapy (IST): the SAA 94 experience. German/Austrian Pediatric Aplastic Anemia Working Group. Klinische Padiatrie, 1998. 210(4): p. 173–9.PubMed
Yamazaki, E., et al., The evidence of clonal evolution with monosomy 7 in aplastic anemia following granulocyte colony-stimulating factor using the polymerase chain reaction. Blood cells, molecules & diseases, 1997. 23(2): p. 213–8.PubMed
Doney, K., et al., Primary treatment of acquired aplastic anemia: outcomes with bone marrow transplantation and immunosuppressive therapy. Seattle Bone Marrow Transplant Team. Annals of internal medicine, 1997. 126(2): p. 107–15.PubMed
Socie, G., et al., Malignant tumors occurring after treatment of aplastic anemia. European Bone Marrow Transplantation-Severe Aplastic Anaemia Working Party. The New England journal of medicine, 1993. 329(16): p. 1152–7.PubMed
Ohga, S., et al., Treatment responses of childhood aplastic anaemia with chromosomal aberrations at diagnosis. British journal of haematology, 2002. 118(1): p. 313–9.PubMed
Mikhailova, N., et al., Cytogenetic abnormalities in patients with severe aplastic anemia. Haematologica, 1996. 81(5): p. 418–22.PubMed
Appelbaum, F.R., et al., Clonal cytogenetic abnormalities in patients with otherwise typical aplastic anemia. Experimental hematology, 1987. 15(11): p. 1134–9.PubMed
Moormeier, J.A., et al., Trisomy 6: a recurring cytogenetic abnormality associated with marrow hypoplasia. Blood, 1991. 77(6): p. 1397–8.PubMed
Kojima, S., et al., Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children. Blood, 2002. 100(3): p. 786–90.PubMed
Bacigalupo, A., et al., Treatment of acquired severe aplastic anemia: bone marrow transplantation compared with immunosuppressive therapy – The European Group for Blood and Marrow Transplantation experience. Seminars in hematology, 2000. 37(1): p. 69–80.
Socie, G., et al., Late clonal diseases of treated aplastic anemia. Seminars in hematology, 2000. 37(1): p. 91–101.PubMed
Piaggio, G., et al., Coexistence of normal and clonal haemopoiesis in aplastic anaemia patients treated with immunosuppressive therapy. British journal of haematology, 1999. 107(3): p. 505–11.PubMed

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