Skip to main content Accessibility help
×
Hostname: page-component-77f85d65b8-9nbrm Total loading time: 0 Render date: 2026-04-14T08:05:42.780Z Has data issue: false hasContentIssue false

16 - Hematologic abnormalities in individuals with Down syndrome

from Section 2 - Neoplastic hematopathology

Published online by Cambridge University Press:  03 May 2011

By
John Kim Choi
Edited by
Maria A. Proytcheva
John Kim Choi
Affiliation:
University of Pennsylvania School of Medicine
Maria A. Proytcheva
Affiliation:
Northwestern University Medical School, Illinois
Get access

Summary

Introduction

Down syndrome (DS) was first reported in 1866 [1], but likely recognized much earlier [2, 3]. DS is caused by an extra copy of chromosome 21 (whole or partial) and is the most common chromosomal abnormality in the live newborn, with a prevalence estimated at 1 in 644–733 births in the United States [4, 5]. This prevalence will likely change because of delayed maternity, which is associated with increased risk of DS [6], and because of simpler and less invasive prenatal diagnosis of DS [7, 8]. Patients with DS have numerous consistent and variable clinical presentations that include mental retardation, characteristic facies, congenital heart defects, and gastrointestinal abnormalities.

The hematologic abnormalities associated with DS and their diagnostic features are detailed in this chapter.

Hematologic abnormalities in the DS newborn

DS newborns can have transient thrombocytopenia, polycythemia, or neutrophilia. They rarely present with unexplained thrombocytosis, anemia, or neutropenia [5], which are most likely unrelated to DS.

Synonyms

Currently, no one has coined a unique term for this phenomenon and it is usually referred to descriptively as hematologic abnormalities in the newborn/neonates with DS [5, 9, 10]. This chapter will use the term hematologic abnormalities in the newborn with DS (HANDS).

Epidemiology

Up to 80%, 66%, and 34% of DS newborns have neutrophilia, thrombocytopenia, and polycythemia, respectively [5, 9, 10]. These hematological abnormalities spontaneously resolve by three weeks of age [9].

Information

Type
Chapter
Information
Diagnostic Pediatric Hematopathology , pp. 310 - 322
Publisher: Cambridge University Press
Print publication year: 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Down, J. Observations on an ethnic classification of idiots. London Hospital Clinical Lectures and Reports. 1866;3:259.Google Scholar
Martinez-Frias, ML. The real earliest historical evidence of Down syndrome. American Journal of Medical Genetics. Part A. 2005;132(2):231.CrossRefGoogle Scholar
Levitas, AS, Reid, CS. An angel with Down syndrome in a sixteenth century Flemish Nativity painting. American Journal of Medical Genetics. Part A. 2003;116(4):399–405.CrossRefGoogle Scholar
Centers for Disease Control and Prevention (CDC). Improved national prevalence estimates for 18 selected major birth defects – United States, 1999–2001. MMWR. Morbidity and Mortality Weekly Report. 2006;54(51):1301–1305.Google Scholar
Henry, E, Walker, D, Wiedmeier, SE, Christensen, RD. Hematological abnormalities during the first week of life among neonates with Down syndrome: data from a multihospital healthcare system. American Journal of Medical Genetics. Part A. 2007;143(1):42–50.CrossRefGoogle Scholar
Hook, EB, Cross, PK, Schreinemachers, DM. Chromosomal abnormality rates at amniocentesis and in live-born infants. JAMA. 1983;249(15):2034–2038.CrossRefGoogle ScholarPubMed
Oudejans, CB, Go, AT, Visser, A, et al. Detection of chromosome 21-encoded mRNA of placental origin in maternal plasma. Clinical Chemistry. 2003;49(9):1445–1449.CrossRefGoogle ScholarPubMed
Wataganara, T, Bianchi, DW. Fetal cell-free nucleic acids in the maternal circulation: new clinical applications. Annals of the New York Academy of Sciences. 2004;1022:90–99.CrossRefGoogle ScholarPubMed
Miller, M, Cosgriff, JM. Hematological abnormalities in newborn infants with Down syndrome. American Journal of Medical Genetics. 1983;16(2):173–177.CrossRefGoogle ScholarPubMed
Hord, JD, Gay, JC, Whitlock, J. Thrombocytopenia in neonates with trisomy 21. Archives of Pediatrics & Adolescent Medicine. 1995;149(7):824–825.CrossRefGoogle ScholarPubMed
Malcovati, L, Della Porta, MG, Lunghi, M, et al. Flow cytometry evaluation of erythroid and myeloid dysplasia in patients with myelodysplastic syndrome. Leukemia. 2005;19(5):776–783.CrossRefGoogle ScholarPubMed
Kussick, SJ, Fromm, JR, Rossini, A, et al. Four-color flow cytometry shows strong concordance with bone marrow morphology and cytogenetics in the evaluation for myelodysplasia. American Journal of Clinical Pathology. 2005;124(2):170–181.CrossRefGoogle ScholarPubMed
Wells, DA, Benesch, M, Loken, MR, et al. Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation. Blood. 2003;102(1):394–403.CrossRefGoogle ScholarPubMed
Ng, PC, Li, G, Chui, KM, et al. Neutrophil CD64 is a sensitive diagnostic marker for early-onset neonatal infection. Pediatric Research. 2004;56(5):796–803.CrossRefGoogle ScholarPubMed
Fjaertoft, G, Hakansson, L, Ewald, U, Foucard, T, Venge, P. Neutrophils from term and preterm newborn infants express the high affinity Fcgamma-receptor I (CD64) during bacterial infections. Pediatric Research. 1999;45(6):871–876.CrossRefGoogle ScholarPubMed
Layseca-Espinosa, E, Perez-Gonzalez, LF, Torres-Montes, A, et al. Expression of CD64 as a potential marker of neonatal sepsis. Pediatric Allergy and Immunology. 2002;13(5):319–327.CrossRefGoogle ScholarPubMed
Skrzeczynska, J, Kobylarz, K, Hartwich, Z, Zembala, M, Pryjma, J. CD14+CD16+ monocytes in the course of sepsis in neonates and small children: monitoring and functional studies. Scandinavian Journal of Immunology. 2002;55(6):629–638.CrossRefGoogle ScholarPubMed
Ng, PC, Li, K, Wong, RP, et al. Neutrophil CD64 expression: a sensitive diagnostic marker for late-onset nosocomial infection in very low birthweight infants. Pediatric Research. 2002;51(3):296–303.CrossRefGoogle ScholarPubMed
Tunstall-Pedoe, O, Roy, A, Karadimitris, A, et al. Abnormalities in the myeloid progenitor compartment in Down syndrome fetal liver precede acquisition of GATA1 mutations. Blood. 2008;112(12):4507–4511.CrossRefGoogle ScholarPubMed
Chou, ST, Opalinska, JB, Yao, Y, et al. Trisomy 21 enhances human fetal erythro-megakaryocytic development. Blood. 2008;112(12):4503–4506.CrossRefGoogle ScholarPubMed
Wiseman, FK, Alford, KA, Tybulewicz, VL, Fisher, EM. Down syndrome – recent progress and future prospects. Human Molecular Genetics. 2009;18(R1):R75–R83.CrossRefGoogle ScholarPubMed
Kirsammer, G, Jilani, S, Liu, H, et al. Highly penetrant myeloproliferative disease in the Ts65Dn mouse model of Down syndrome. Blood. 2008;111(2):767–775.CrossRefGoogle ScholarPubMed
Robertson, M, Jong, G, Mansvelt, E. Prenatal diagnosis of congenital leukemia in a fetus at 25 weeks' gestation with Down syndrome: case report and review of the literature. Ultrasound in Obstetrics & Gynecology. 2003;21(5):486–489.CrossRefGoogle Scholar
Smrcek, JM, Baschat, AA, Germer, U, Gloeckner-Hofmann, K, Gembruch, U. Fetal hydrops and hepatosplenomegaly in the second half of pregnancy: a sign of myeloproliferative disorder in fetuses with trisomy 21. Ultrasound in Obstetrics & Gynecology. 2001;17(5):403–409.CrossRefGoogle ScholarPubMed
Zerres, K, Schwanitz, G, Niesen, M, et al. Prenatal diagnosis of acute non-lymphoblastic leukaemia in Down syndrome. Lancet. 1990;335(8681):117.CrossRefGoogle ScholarPubMed
Won, RH, Currier, RJ, Lorey, F, Towner, DR. The timing of demise in fetuses with trisomy 21 and trisomy 18. Prenatal Diagnosis. 2005;25(7):608–611.CrossRefGoogle ScholarPubMed
Swerdlow, SH, Campo, E, Harris, NL, et al. (eds.). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (4th edn.). Lyon: IARC Press; 2008, 439.Google Scholar
Zipursky, A, Brown, E, Christensen, H, Sutherland, R, Doyle, J. Leukemia and/or myeloproliferative syndrome in neonates with Down syndrome. Seminars in Perinatology. 1997;21(1):97–101.CrossRefGoogle ScholarPubMed
Zipursky, A, Brown, EJ, Christensen, H, Doyle, J. Transient myeloproliferative disorder (transient leukemia) and hematologic manifestations of Down syndrome. Clinics in Laboratory Medicine. 1999;19(1):157–167, vii.Google ScholarPubMed
Awasthi, A, Das, R, Varma, N, et al. Hematological disorders in Down syndrome: ten-year experience at a Tertiary Care Centre in North India. Pediatric Hematology and Oncology. 2005;22(6):507–512.CrossRefGoogle Scholar
Pine, SR, Guo, Q, Yin, C, et al. Incidence and clinical implications of GATA1 mutations in newborns with Down syndrome. Blood. 2007;110(6):2128–2131.CrossRefGoogle ScholarPubMed
Massey, GV, Zipursky, A, Chang, MN, et al. A prospective study of the natural history of transient leukemia (TL) in neonates with Down syndrome (DS): Children's Oncology Group (COG) study POG-9481. Blood. 2006;107(12):4606–4613.CrossRefGoogle ScholarPubMed
Muramatsu, H, Kato, K, Watanabe, N, et al. Risk factors for early death in neonates with Down syndrome and transient leukaemia. British Journal of Haematology. 2008;142(4):610–615.CrossRefGoogle ScholarPubMed
Klusmann, JH, Creutzig, U, Zimmermann, M, et al. Treatment and prognostic impact of transient leukemia in neonates with Down syndrome. Blood. 2008;111(6):2991–2998.CrossRefGoogle ScholarPubMed
Miyauchi, J, Ito, Y, Kawano, T, Tsunematsu, Y, Shimizu, K. Unusual diffuse liver fibrosis accompanying transient myeloproliferative disorder in Down's syndrome: a report of four autopsy cases and proposal of a hypothesis. Blood. 1992;80(6):1521–1527.Google ScholarPubMed
Ruchelli, ED, Uri, A, Dimmick, JE, et al. Severe perinatal liver disease and Down syndrome: an apparent relationship. Human Pathology. 1991;22(12):1274–8120.CrossRefGoogle Scholar
Jaffe, ES, Harris, NL, Stein, H, Vardiman, J. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press; 2001, 351.Google Scholar
Weinstein, HJ. Congenital leukaemia and the neonatal myeloproliferative disorders associated with Down's syndrome. Clinics in Haematology. 1978;7(1):147–154.Google ScholarPubMed
Ross, JD, Moloney, WC, Desforges, JF. Ineffective regulation of granulopoiesis masquerading as congenital leukemia in a mongoloid child. Journal of Pediatrics. 1963;63:1–10.CrossRefGoogle Scholar
Hayhoe, FG, Quaglino, D. Haematological Cytochemistry (3rd edn.). New York: Churchill Livingston; 1994, 673.Google Scholar
Eguchi, M, Sakaibara, H, Suda, J, et al. Ultrastructural and ultracytochemical differences between transient myeloproliferative disorder and megakaryoblastic leukaemia in Down's syndrome. British Journal of Haematology. 1989;73(3):315–322.CrossRefGoogle ScholarPubMed
Simon, JH, Tebbi, CK, Freeman, AI, et al. Acute megakaryoblastic leukemia associated with mosaic Down's syndrome. Cancer. 1987;60(10):2515–2520.3.0.CO;2-F>CrossRefGoogle ScholarPubMed
Kalousek, DK, Chan, KW. Transient myeloproliferative disorder in chromosomally normal newborn infant. Medical and Pediatric Oncology. 1987;15(1):38–41.CrossRefGoogle ScholarPubMed
Doyle, JJ, Thorner, P, Poon, A, et al. Transient leukemia followed by megakaryoblastic leukemia in a child with mosaic Down syndrome. Leukemia & Lymphoma. 1995;17(3–4):345–350.CrossRefGoogle Scholar
Karandikar, NJ, Aquino, DB, McKenna, RW, Kroft, SH. Transient myeloproliferative disorder and acute myeloid leukemia in Down syndrome. An immunophenotypic analysis. American Journal of Clinical Pathology. 2001;116(2):204–210.CrossRefGoogle ScholarPubMed
Duchayne, E, Fenneteau, O, Pages, MP, et al. Acute megakaryoblastic leukaemia: a national clinical and biological study of 53 adult and childhood cases by the Groupe Français d'Hématologie Cellulaire (GFHC). Leukemia & Lymphoma. 2003;44(1):49–58.CrossRefGoogle Scholar
Betz, SA, Foucar, K, Head, DR, Chen, IM, Willman, CL. False-positive flow cytometric platelet glycoprotein IIb/IIIa expression in myeloid leukemias secondary to platelet adherence to blasts. Blood. 1992;79(9):2399–2403.Google ScholarPubMed
Greene, ME, Mundschau, G, Wechsler, J, et al. Mutations in GATA1 in both transient myeloproliferative disorder and acute megakaryoblastic leukemia of Down syndrome. Blood Cells, Molecules, and Diseases. 2003;31(3):351–356.CrossRefGoogle ScholarPubMed
Orkin, SH. Hematopoiesis: how does it happen?Current Opinion in Cell Biology. 1995;7(6):870–877.CrossRefGoogle ScholarPubMed
Carpenter, E, Valverde-Garduno, V, Sternberg, A, et al. GATA1 mutation and trisomy 21 are required only in haematopoietic cells for development of transient myeloproliferative disorder. British Journal of Haematology. 2005;128(4):548–551.CrossRefGoogle ScholarPubMed
Cushing, T, Clericuzio, CL, Wilson, CS, et al. Risk for leukemia in infants without Down syndrome who have transient myeloproliferative disorder. Journal of Pediatrics. 2006;148(5):687–689.CrossRefGoogle ScholarPubMed
Vita, S, Mulligan, C, McElwaine, S, et al. Loss-of-function JAK3 mutations in TMD and AMKL of Down syndrome. British Journal of Haematology. 2007;137(4):337–341.CrossRefGoogle ScholarPubMed
Kiyoi, H, Yamaji, S, Kojima, S, Naoe, T. JAK3 mutations occur in acute megakaryoblastic leukemia both in Down syndrome children and non-Down syndrome adults. Leukemia. 2007;21(3):574–576.CrossRefGoogle ScholarPubMed
Homans, AC, Verissimo, AM, Vlacha, V. Transient abnormal myelopoiesis of infancy associated with trisomy 21. The American Journal of Pediatric Hematology/Oncology. 1993;15(4):392–399.Google ScholarPubMed
Isaacs, H. Fetal and neonatal leukemia. Journal of Pediatric Hematology/Oncology. 2003;25(5):348–361.CrossRefGoogle ScholarPubMed
Fong, CT, Brodeur, GM. Down's syndrome and leukemia: epidemiology, genetics, cytogenetics and mechanisms of leukemogenesis. Cancer Genetics and Cytogenetics. 1987;28(1):55–76.CrossRefGoogle ScholarPubMed
Robison, LL, Nesbit, ME., Sather, HN, et al. Down syndrome and acute leukemia in children: a 10-year retrospective survey from Childrens Cancer Study Group. Journal of Pediatrics. 1984;105(2):235–242.CrossRefGoogle ScholarPubMed
Creutzig, U, Ritter, J, Vormoor, J, et al. Myelodysplasia and acute myelogenous leukemia in Down's syndrome. A report of 40 children of the AML-BFM Study Group. Leukemia. 1996;10(11):1677–1686.Google ScholarPubMed
Lange, BJ, Kobrinsky, N, Barnard, DR, et al. Distinctive demography, biology, and outcome of acute myeloid leukemia and myelodysplastic syndrome in children with Down syndrome: Children's Cancer Group Studies 2861 and 2891. Blood. 1998;91(2):608–615.Google ScholarPubMed
Forestier, E, Izraeli, S, Beverloo, B, et al. Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome: an iBFM-SG study. Blood. 2008;111(3):1575–1583.CrossRefGoogle ScholarPubMed
Ross, JA, Spector, LG, Robison, LL, Olshan, AF. Epidemiology of leukemia in children with Down syndrome. Pediatric Blood and Cancer. 2005;44(1):8–12.CrossRefGoogle ScholarPubMed
Lange, B. The management of neoplastic disorders of haematopoiesis in children with Down's syndrome. British Journal of Haematology. 2000;110(3):512–524.CrossRefGoogle ScholarPubMed
Hasle, H. Pattern of malignant disorders in individuals with Down's syndrome. The Lancet Oncology. 2001;2(7):429–436.CrossRefGoogle ScholarPubMed
Whitlock, JA, Sather, HN, Gaynon, P, et al. Clinical characteristics and outcome of children with Down syndrome and acute lymphoblastic leukemia: a Children's Cancer Group study. Blood. 2005;106(13):4043–4049.CrossRefGoogle ScholarPubMed
Ravindranath, Y, Abella, E, Krischer, JP, et al. Acute myeloid leukemia (AML) in Down's syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498. Blood. 1992;80(9):2210–2214.Google ScholarPubMed
Kuerbitz, SJ, Civin, CI, Krischer, JP, et al. Expression of myeloid-associated and lymphoid-associated cell-surface antigens in acute myeloid leukemia of childhood: a Pediatric Oncology Group study. Journal of Clinical Oncology. 1992;10(9):1419–1429.CrossRefGoogle ScholarPubMed
Creutzig, U, Harbott, J, Sperling, C, et al. Clinical significance of surface antigen expression in children with acute myeloid leukemia: results of study AML-BFM-87. Blood. 1995;86(8):3097–3108.Google ScholarPubMed
Levitt, GA, Stiller, CA, Chessells, JM. Prognosis of Down's syndrome with acute leukaemia. Archives of Disease in Childhood. 1990;65(2):212–216.CrossRefGoogle ScholarPubMed
Hasle, H, Abrahamsson, J, Arola, M, et al. Myeloid leukemia in children 4 years or older with Down syndrome often lacks GATA1 mutation and cytogenetics and risk of relapse are more akin to sporadic AML. Leukemia. 2008;22(7):1428–1430.CrossRefGoogle ScholarPubMed
Yumura-Yagi, K, Hara, J, Kurahashi, H, et al. Mixed phenotype of blasts in acute megakaryocytic leukaemia and transient abnormal myelopoiesis in Down's syndrome. British Journal of Haematology. 1992;81(4):520–525.CrossRefGoogle ScholarPubMed
Litz, CE, Davies, S, Brunning, RD, et al. Acute leukemia and the transient myeloproliferative disorder associated with Down syndrome: morphologic, immunophenotypic and cytogenetic manifestations. Leukemia. 1995;9(9):1432–1439.Google ScholarPubMed
Ragab, AH, Abdel-Mageed, A, Shuster, JJ, et al. Clinical characteristics and treatment outcome of children with acute lymphocytic leukemia and Down's syndrome. A Pediatric Oncology Group study. Cancer. 1991;67(4):1057–1063.3.0.CO;2-K>CrossRefGoogle ScholarPubMed
Dordelmann, M, Schrappe, M, Reiter, A, et al. Down's syndrome in childhood acute lymphoblastic leukemia: clinical characteristics and treatment outcome in four consecutive BFM trials. Berlin-Frankfurt-Munster Group. Leukemia. 1998;12(5):645–651.CrossRefGoogle ScholarPubMed
Ma, Z, Morris, SW, Valentine, V, et al. Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nature Genetics. 2001;28(3):220–221.CrossRefGoogle Scholar
Mercher, T, Busson-Le, Coniat M, Khac, FN, et al. Recurrence of OTT-MAL fusion in t(1;22) of infant AML-M7. Genes, Chromosomes & Cancer. 2002;33(1):22–28.CrossRefGoogle Scholar
Vyas, P, Crispino, JD. Molecular insights into Down syndrome-associated leukemia. Current Opinion in Pediatrics. 2007;19(1):9–14.CrossRefGoogle ScholarPubMed
Malinge, S, Ragu, C, Della-Valle, V, et al. Activating mutations in human acute megakaryoblastic leukemia. Blood. 2008;112(10):4220–4226.CrossRefGoogle ScholarPubMed
Walters, DK, Mercher, T, Gu, TL, et al. Activating alleles of JAK3 in acute megakaryoblastic leukemia. Cancer Cell. 2006;10(1):65–75.CrossRefGoogle ScholarPubMed
Lightfoot, J, Hitzler, JK, Zipursky, A, Albert, M, Macgregor, PF. Distinct gene signatures of transient and acute megakaryoblastic leukemia in Down syndrome. Leukemia. 2004;18(10):1617–1623.CrossRefGoogle ScholarPubMed
McElwaine, S, Mulligan, C, Groet, J, et al. Microarray transcript profiling distinguishes the transient from the acute type of megakaryoblastic leukaemia (M7) in Down's syndrome, revealing PRAME as a specific discriminating marker. British Journal of Haematology. 2004;125(6):729–742.CrossRefGoogle ScholarPubMed
Bourquin, JP, Subramanian, A, Langebrake, C, et al. Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(9):3339–3344.CrossRefGoogle ScholarPubMed
Ge, Y, Dombkowski, AA, LaFiura, KM, et al. Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia. Blood. 2006;107(4):1570–1581.CrossRefGoogle ScholarPubMed
Berger, R. Acute lymphoblastic leukemia and chromosome 21. Cancer Genetics and Cytogenetics. 1997;94(1):8–12.CrossRefGoogle ScholarPubMed
Bassal, M, La, MK, Whitlock, JA, et al. Lymphoblast biology and outcome among children with Down syndrome and ALL treated on CCG-1952. Pediatric Blood and Cancer. 2005;44(1):21–28.CrossRefGoogle ScholarPubMed
Pui, CH, Raimondi, SC, Borowitz, MJ, et al. Immunophenotypes and karyotypes of leukemic cells in children with Down syndrome and acute lymphoblastic leukemia. Journal of Clinical Oncology. 1993;11(7):1361–1367.CrossRefGoogle ScholarPubMed
Lundin, C, Heldrup, J, Ahlgren, T, Olofsson, T, Johansson, B. B-cell precursor t(8;14)(q11;q32)-positive acute lymphoblastic leukemia in children is strongly associated with Down syndrome or with a concomitant Philadelphia chromosome. European Journal of Haematology. 2009;82(1):46–53.CrossRefGoogle Scholar
Kearney, L, Gonzalez, Castro D, Yeung, J, et al. Specific JAK2 mutation (JAK2R683) and multiple gene deletions in Down syndrome acute lymphoblastic leukemia. Blood. 2009;113(3):646–648.CrossRefGoogle ScholarPubMed
Malinge, S, Ben-Abdelali, R, Settegrana, C, et al. Novel activating JAK2 mutation in a patient with Down syndrome and B-cell precursor acute lymphoblastic leukemia. Blood. 2007;109(5):2202–2204.CrossRefGoogle Scholar
Bercovich, D, Ganmore, I, Scott, LM, et al. Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome. Lancet. 2008;372(9648):1484–1492.CrossRefGoogle ScholarPubMed
Malinge, S, Izraeli, S, Crispino, JD. Insights into the manifestations, outcomes, and mechanisms of leukemogenesis in Down syndrome. Blood. 2009;113(12):2619–2628.CrossRefGoogle ScholarPubMed
Vyas, P, Roberts, I. Down myeloid disorders: a paradigm for childhood preleukaemia and leukaemia and insights into normal megakaryopoiesis. Early Human Development. 2006;82(12):767–773.CrossRefGoogle ScholarPubMed
Gamis, AS. Acute myeloid leukemia and Down syndrome evolution of modern therapy – state of the art review. Pediatric Blood and Cancer. 2005;44(1):13–20.CrossRefGoogle ScholarPubMed
Zwaan, CM, Kaspers, GJ, Pieters, R, et al. Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome. Blood. 2002;99(1):245–251.CrossRefGoogle ScholarPubMed
Ge, Y, Stout, ML, Tatman, DA, et al. GATA1, cytidine deaminase, and the high cure rate of Down syndrome children with acute megakaryocytic leukemia. Journal of the National Cancer Institute. 2005;97(3):226–231.CrossRefGoogle ScholarPubMed
Taub, JW, Huang, X, Matherly, LH, et al. Expression of chromosome 21-localized genes in acute myeloid leukemia: differences between Down syndrome and non-Down syndrome blast cells and relationship to in vitro sensitivity to cytosine arabinoside and daunorubicin. Blood. 1999;94(4):1393–1400.Google ScholarPubMed
Hasle, H, Niemeyer, CM, Chessells, JM, et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia. 2003;17(2):277–282.CrossRefGoogle ScholarPubMed
Zipursky, A, Thorner, P, Harven, E, Christensen, H, Doyle, J. Myelodysplasia and acute megakaryoblastic leukemia in Down's syndrome. Leukemia Research. 1994;18(3):163–171.CrossRefGoogle ScholarPubMed

Accessibility standard: Unknown

Why this information is here

This section outlines the accessibility features of this content - including support for screen readers, full keyboard navigation and high-contrast display options. This may not be relevant for you.

Accessibility Information

Accessibility compliance for the PDF of this chapter is currently unknown and may be updated in the future.

Save book to Kindle

To save this book to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×