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Published in: Annals of Hematology 1/2005

01-12-2005 | Original Article

The hematopathological basis for studying effects of the demethylating agent 5-aza-2′-deoxycytidine (decitabine) in myelodysplasia

Authors: Hans Eckart Schaefer, Michael Lübbert

Published in: Annals of Hematology | Special Issue 1/2005

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Abstract

The myelodysplastic syndromes have, since their first recognition decades ago, been considered notoriously difficult with regard to their proper classification, determination of prognosis, and optimal treatment. With the advent of the French–American–British (FAB) classification, now aided but not superseded by the World Health Organization classification, distinct biological entities have been delineated, which in turn are very useful for stratification to different, established and experimental treatment modalities. However, precise subclassification of different types of myelodysplastic syndrome (MDS) is only possible with hematopathological studies based on the analysis of peripheral blood, bone marrow smear, and bone marrow biopsy, backed by appropriate clinical information. Bone marrow cytogenetics are also essential for any risk stratification since they still provide the second most powerful prognostic parameter after bone marrow blast enumeration. This paper will review the most important aspects of hematopathological diagnostics in MDS, risk scoring, and their application to the inclusion and stratification of patients into the European Organization for Research and Treatment of Cancer (EORTC)/German MDS Study Group Phase III multicenter trial of low-dose decitabine in patients more than 60 years old with high-risk MDS. Emphasis is placed on itemizing the broad spectrum of cytologic and histologic stigmata defining the myelodysplastic categories that are to be considered in this study.
Literature
1.
go back to reference Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C (1982) Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51:189–199PubMed Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C (1982) Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51:189–199PubMed
2.
go back to reference Bennett JM (2000) World Health Organization classification of the acute leukemias and myelodysplastic syndrome. Int J Hematol 72:131–133PubMed Bennett JM (2000) World Health Organization classification of the acute leukemias and myelodysplastic syndrome. Int J Hematol 72:131–133PubMed
3.
go back to reference van den Berghe H, Cassiman J-J, David G, Fryns J-P, Michaux J-L, Sokal G (1974) Distinct haematological disorder with deletion of long arm of No. 5 chromosome. Nature 251:437–438CrossRefPubMed van den Berghe H, Cassiman J-J, David G, Fryns J-P, Michaux J-L, Sokal G (1974) Distinct haematological disorder with deletion of long arm of No. 5 chromosome. Nature 251:437–438CrossRefPubMed
4.
go back to reference Bessis M (1977) Blood smears reinterpreted. Springer, Berlin Heidelberg New York Bessis M (1977) Blood smears reinterpreted. Springer, Berlin Heidelberg New York
5.
go back to reference van den Bosch J, Lübbert M, Verhoef G, Wijermans PW (2004) The effects of 5-aza-2′-deoxycytidine (decitabine) on the platelet count in patients with inter-mediate and high-risk myelodysplastic syndromes. Leuk Res 28:785–790CrossRefPubMed van den Bosch J, Lübbert M, Verhoef G, Wijermans PW (2004) The effects of 5-aza-2′-deoxycytidine (decitabine) on the platelet count in patients with inter-mediate and high-risk myelodysplastic syndromes. Leuk Res 28:785–790CrossRefPubMed
6.
go back to reference Bowen D, Culligan D, Jowitt S, Kelsey S, Mufti G, Oscier D, Parker J; UK MDS Guidelines Group (2003) Guidelines for the diagnosis and therapy of adult myelodysplastic syndromes. Br J Haematol 120:187–200CrossRefPubMed Bowen D, Culligan D, Jowitt S, Kelsey S, Mufti G, Oscier D, Parker J; UK MDS Guidelines Group (2003) Guidelines for the diagnosis and therapy of adult myelodysplastic syndromes. Br J Haematol 120:187–200CrossRefPubMed
7.
go back to reference Castoldi GL (2003) The myelodysplastic syndromes. In: Zucker-Franklin D, Grossi CE (eds) An atlas of blood cells, function and pathology, 3rd edn. Edi-Ermes, Milan Castoldi GL (2003) The myelodysplastic syndromes. In: Zucker-Franklin D, Grossi CE (eds) An atlas of blood cells, function and pathology, 3rd edn. Edi-Ermes, Milan
8.
go back to reference Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, Löwenberg B, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Wijermans PW, Gore S, Greenberg PL (2000) World Health Organization (WHO) International Working Group. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 96:3671–3674PubMed Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, Löwenberg B, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Wijermans PW, Gore S, Greenberg PL (2000) World Health Organization (WHO) International Working Group. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 96:3671–3674PubMed
9.
go back to reference Cheson BD, Bennett JM, Kantarjian H, Schiffer CA, Nimer SD, Löwenberg B, Stone RM, Mittelman M, Sanz GF, Wijermans PW, Greenberg PL (2001) Myelodysplastic syndromes standardized response criteria; further definition. Blood 98:1985CrossRefPubMed Cheson BD, Bennett JM, Kantarjian H, Schiffer CA, Nimer SD, Löwenberg B, Stone RM, Mittelman M, Sanz GF, Wijermans PW, Greenberg PL (2001) Myelodysplastic syndromes standardized response criteria; further definition. Blood 98:1985CrossRefPubMed
10.
go back to reference Claus R, Almstedt M, Lübbert M (2005) Epigenetic treatment of hematopoietic malignancies: in vivo targets of demethylating agents. Semin Oncol 32:511–520CrossRefPubMed Claus R, Almstedt M, Lübbert M (2005) Epigenetic treatment of hematopoietic malignancies: in vivo targets of demethylating agents. Semin Oncol 32:511–520CrossRefPubMed
11.
go back to reference Daskalakis M, Nguyen TT, Nguyen C, Guldberg P, Köhler G, Wijermans P, Jones PA, Lübbert M (2002) Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-aza-2’-deoxycytidine (decitabine) treatment. Blood 100:2957–2964CrossRefPubMed Daskalakis M, Nguyen TT, Nguyen C, Guldberg P, Köhler G, Wijermans P, Jones PA, Lübbert M (2002) Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-aza-2’-deoxycytidine (decitabine) treatment. Blood 100:2957–2964CrossRefPubMed
12.
go back to reference Davis AT, Brunning RD, Quie PG (1971) Polymorphonuclear leukocyte myeloperoxidase deficiency in a patient with myelomonocytic leukemia. N Engl J Med 285:789–790PubMedCrossRef Davis AT, Brunning RD, Quie PG (1971) Polymorphonuclear leukocyte myeloperoxidase deficiency in a patient with myelomonocytic leukemia. N Engl J Med 285:789–790PubMedCrossRef
13.
go back to reference Gassmann W (2004) Morphological leukemia diagnostics in the competence net for acute and chronic leukemias. Med Welt 55:256–260 Gassmann W (2004) Morphological leukemia diagnostics in the competence net for acute and chronic leukemias. Med Welt 55:256–260
14.
go back to reference Gattermann N, Retzlaff S, Wang YL, Hofhaus G, Heinisch J, Aul C, Schneider W (1997) Heteroplasmic point mutations of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia. Blood 90:4961–4972PubMed Gattermann N, Retzlaff S, Wang YL, Hofhaus G, Heinisch J, Aul C, Schneider W (1997) Heteroplasmic point mutations of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia. Blood 90:4961–4972PubMed
15.
go back to reference Germing U, Gattermann N, Strupp C, Aivado M, Aul C (2000) Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res 24:983–992CrossRefPubMed Germing U, Gattermann N, Strupp C, Aivado M, Aul C (2000) Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res 24:983–992CrossRefPubMed
16.
go back to reference Germing U, Gattermann N (2001) Refractory anemia with excess of blasts in transformation: a dying category? Leuk Res 25:1095–1096CrossRefPubMed Germing U, Gattermann N (2001) Refractory anemia with excess of blasts in transformation: a dying category? Leuk Res 25:1095–1096CrossRefPubMed
17.
go back to reference Giagounidis AA, Germing U, Haase D, Hildebrandt B, Schlegelberger B, Schoch C, Wilkens L, Heinsch M, Willems H, Aivado M, Aul C (2004) Clinical, morphological, cytogenetic, and prognostic features of patients with myelodysplastic syndromes and del(5q) including band q31. Leukemia 18:113–119CrossRefPubMed Giagounidis AA, Germing U, Haase D, Hildebrandt B, Schlegelberger B, Schoch C, Wilkens L, Heinsch M, Willems H, Aivado M, Aul C (2004) Clinical, morphological, cytogenetic, and prognostic features of patients with myelodysplastic syndromes and del(5q) including band q31. Leukemia 18:113–119CrossRefPubMed
18.
go back to reference Greenberg P, Cox C, Le Beau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079–2088PubMed Greenberg P, Cox C, Le Beau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079–2088PubMed
19.
go back to reference Greenberg P, Anderson J, de Witte T, Estey E, Fenaux P, Gupta P, Hamblin T, Hellström-Lindberg E, List A, Mufti G, Neuwirtova R, Ohyashiki K, Oscier D, Sanz G, Sanz M, Willman C (2000) Problematic WHO reclassification of myelodysplastic syndromes. Members of the International MDS Study Group. J Clin Oncol 18:3447–3452PubMed Greenberg P, Anderson J, de Witte T, Estey E, Fenaux P, Gupta P, Hamblin T, Hellström-Lindberg E, List A, Mufti G, Neuwirtova R, Ohyashiki K, Oscier D, Sanz G, Sanz M, Willman C (2000) Problematic WHO reclassification of myelodysplastic syndromes. Members of the International MDS Study Group. J Clin Oncol 18:3447–3452PubMed
20.
go back to reference Gupta R, Abdalla SH, Bain BJ (1999) Thrombocytosis with sideroblastic erythropoiesis: a mixed myeloproliferative myelodysplastic syndrome. Leuk Lymphoma 34:615–619PubMed Gupta R, Abdalla SH, Bain BJ (1999) Thrombocytosis with sideroblastic erythropoiesis: a mixed myeloproliferative myelodysplastic syndrome. Leuk Lymphoma 34:615–619PubMed
21.
go back to reference Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349:2042–2054CrossRefPubMed Herman JG, Baylin SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349:2042–2054CrossRefPubMed
22.
23.
go back to reference Issa JP, Garcia-Manero G, Giles FJ, Mannari R, Thomas D, Faderl S, Bayar E, Lyons J, Rosenfeld CS, Cortes J, Kantarjian HM (2004) Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 103:1635–1640CrossRefPubMed Issa JP, Garcia-Manero G, Giles FJ, Mannari R, Thomas D, Faderl S, Bayar E, Lyons J, Rosenfeld CS, Cortes J, Kantarjian HM (2004) Phase 1 study of low-dose prolonged exposure schedules of the hypomethylating agent 5-aza-2′-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 103:1635–1640CrossRefPubMed
24.
go back to reference Jaffe ES, Lee Harris N, Stein H, Vardiman JW (eds) (2001) Pathology and genetics of tumours of haematopoietic and lymphoid tissues. IARC, Lyon Jaffe ES, Lee Harris N, Stein H, Vardiman JW (eds) (2001) Pathology and genetics of tumours of haematopoietic and lymphoid tissues. IARC, Lyon
25.
go back to reference Juneja SK, Imbert M, Jouault H, Scoazec JY, Sigaux F, Sultan C (1983) Haematological features of primary myelodysplastic syndromes (PMDS) at initial presentation: a study of 118 cases. J Clin Pathol 36:1129–1135PubMedCrossRef Juneja SK, Imbert M, Jouault H, Scoazec JY, Sigaux F, Sultan C (1983) Haematological features of primary myelodysplastic syndromes (PMDS) at initial presentation: a study of 118 cases. J Clin Pathol 36:1129–1135PubMedCrossRef
26.
go back to reference Koike T, Uesugi Y, Toba K, Narita M, Fuse I, Takahashi M, Shibata A (1995) 5q-minus-syndrome presenting as essential thrombocythemia myelodysplastic syndrome or chronic myeloproliferative disorders? Leukemia 9:517–518PubMed Koike T, Uesugi Y, Toba K, Narita M, Fuse I, Takahashi M, Shibata A (1995) 5q-minus-syndrome presenting as essential thrombocythemia myelodysplastic syndrome or chronic myeloproliferative disorders? Leukemia 9:517–518PubMed
27.
go back to reference List A, Kurtin S, Roe DJ, Buresh A, Mahadevan D, Fuchs D, Rimsza L, Heaton R, Knight R, Zeldis JB (2005) Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 352:549–557CrossRefPubMed List A, Kurtin S, Roe DJ, Buresh A, Mahadevan D, Fuchs D, Rimsza L, Heaton R, Knight R, Zeldis JB (2005) Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 352:549–557CrossRefPubMed
28.
go back to reference Löffler H, Rastetter J, Haferlach T (2004) Atlas der klinischen Hämatologie, 6th edn. Springer, Berlin Heidelberg New York Löffler H, Rastetter J, Haferlach T (2004) Atlas der klinischen Hämatologie, 6th edn. Springer, Berlin Heidelberg New York
29.
go back to reference Lübbert M, Wijermans PW, Kunzmann R, Verhoef G, Bosly A, Ravoet C, Andre M, Ferrant A (2001) Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Br J Haematol 114:349–357CrossRefPubMed Lübbert M, Wijermans PW, Kunzmann R, Verhoef G, Bosly A, Ravoet C, Andre M, Ferrant A (2001) Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Br J Haematol 114:349–357CrossRefPubMed
30.
go back to reference Mahmood T, Robinson WA, Hamstra RD, Wallner SF (1979) Macrocytic anemia, thrombocytosis and nonlobulated megakaryocytes in the 5q− syndrome, a distinct entity. Am J Med 66:946–950CrossRefPubMed Mahmood T, Robinson WA, Hamstra RD, Wallner SF (1979) Macrocytic anemia, thrombocytosis and nonlobulated megakaryocytes in the 5q− syndrome, a distinct entity. Am J Med 66:946–950CrossRefPubMed
31.
go back to reference Mufti GJ, Flandrin G, Schaefer HE, Sandberg AA, Kanfer EJ (1996) An atlas of malignant haematology. Cytology, histology and cytogenetics. Dunitz, London Mufti GJ, Flandrin G, Schaefer HE, Sandberg AA, Kanfer EJ (1996) An atlas of malignant haematology. Cytology, histology and cytogenetics. Dunitz, London
32.
go back to reference Murphy S (1993) Thrombocytosis and thrombocythaemia. Clin Haematol 12:89–106 Murphy S (1993) Thrombocytosis and thrombocythaemia. Clin Haematol 12:89–106
33.
go back to reference Naegeli O (1931) Blutkrankheiten und Blutdiagnostik, 5th edn. Leipzig, Veit & Co., Berlin, pp 1907–1908 Naegeli O (1931) Blutkrankheiten und Blutdiagnostik, 5th edn. Leipzig, Veit & Co., Berlin, pp 1907–1908
34.
go back to reference Nagai K, Kohno T, Chen YX, Tsushima H, Mori H, Nakamura H, Jinnai I, Matsuo T, Kuriyama K, Tomonaga M, Bennett JM (1996) Diagnostic criteria for hypocellular acute leukemia, a clinical entity distinct from overt acute leukemia and myelodysplastic syndrome. Leuk Res 20:563–574CrossRefPubMed Nagai K, Kohno T, Chen YX, Tsushima H, Mori H, Nakamura H, Jinnai I, Matsuo T, Kuriyama K, Tomonaga M, Bennett JM (1996) Diagnostic criteria for hypocellular acute leukemia, a clinical entity distinct from overt acute leukemia and myelodysplastic syndrome. Leuk Res 20:563–574CrossRefPubMed
35.
go back to reference Schaefer HE (1990) Zytologische Hämatopathologie unter besonderer Berücksichtigung histochemischer Methoden. Beitr Onkol 38:196–260 Schaefer HE (1990) Zytologische Hämatopathologie unter besonderer Berücksichtigung histochemischer Methoden. Beitr Onkol 38:196–260
36.
go back to reference Schaefer HE (2005) Die histologische Diagnostik an Beckenkammbiopsien. In: Haferlach T (ed) Labordiagnostik bei Leukämien und Lymphomen. UNI-MED, Bremen, pp 32–72 Schaefer HE (2005) Die histologische Diagnostik an Beckenkammbiopsien. In: Haferlach T (ed) Labordiagnostik bei Leukämien und Lymphomen. UNI-MED, Bremen, pp 32–72
37.
go back to reference Schaefer HE, Fischer R (1970) Peroxydaseaktivität als Ursache der stabilen Sudanophilie in Granulozyten. Klin Wochenschr 48:1424–1425CrossRefPubMed Schaefer HE, Fischer R (1970) Peroxydaseaktivität als Ursache der stabilen Sudanophilie in Granulozyten. Klin Wochenschr 48:1424–1425CrossRefPubMed
38.
go back to reference Schaefer HE, Weller P, Lansch D (1983) Erworbene und ererbte Defektformen der granulozytären Peroxidase (POX). Acta Histochem 28:219–234 Schaefer HE, Weller P, Lansch D (1983) Erworbene und ererbte Defektformen der granulozytären Peroxidase (POX). Acta Histochem 28:219–234
39.
go back to reference Schmalzl F, Lederer B, Braunsteiner H (1970) Atypical myeloblastic leukemia with differentiation into “paraneutrophils”. Blut (Berl) 20:337–349 Schmalzl F, Lederer B, Braunsteiner H (1970) Atypical myeloblastic leukemia with differentiation into “paraneutrophils”. Blut (Berl) 20:337–349
40.
go back to reference Schmalzl F, Wiedemann C (1983) Zur Technik quantitativer enzymzytochemischer Untersuchungen an polymorphkernigen Neutrophilen des Menschen. Acta Histochem 28:157–162 Schmalzl F, Wiedemann C (1983) Zur Technik quantitativer enzymzytochemischer Untersuchungen an polymorphkernigen Neutrophilen des Menschen. Acta Histochem 28:157–162
41.
go back to reference Swolin B, Weinfeld A, Ridell B, Waldenström J, Westin J (1981) On the 5q− deletion: clinical and cytogenetic observations in ten patients and review of the literature. Blood 58:986–993PubMed Swolin B, Weinfeld A, Ridell B, Waldenström J, Westin J (1981) On the 5q− deletion: clinical and cytogenetic observations in ten patients and review of the literature. Blood 58:986–993PubMed
42.
go back to reference Steensma DP, Gibbons RJ, Higgs DR (2005) Acquired alpha-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies. Blood 105:443–52CrossRefPubMed Steensma DP, Gibbons RJ, Higgs DR (2005) Acquired alpha-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies. Blood 105:443–52CrossRefPubMed
43.
go back to reference Thiele J, Schmitz B, Gross H, Kvasnicka HM, Niederle N, Leder LD, Fischer R (1997) Fluorescence in situ hybridization (FISH) reveals that in chronic myelogenous leukaemia (CML) following interferon alpha therapy, normalization of megakaryocyte size is associated with the loss of bcr/abl translocation. Histopathology 31:215–221CrossRefPubMed Thiele J, Schmitz B, Gross H, Kvasnicka HM, Niederle N, Leder LD, Fischer R (1997) Fluorescence in situ hybridization (FISH) reveals that in chronic myelogenous leukaemia (CML) following interferon alpha therapy, normalization of megakaryocyte size is associated with the loss of bcr/abl translocation. Histopathology 31:215–221CrossRefPubMed
44.
go back to reference Wells DA, Benesch M, Loken MR, Vallejo C, Myerson D, Leisenring WM, Deeg HJ (2003) 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 102:394–403CrossRefPubMed Wells DA, Benesch M, Loken MR, Vallejo C, Myerson D, Leisenring WM, Deeg HJ (2003) 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 102:394–403CrossRefPubMed
45.
go back to reference Wheeler LA, Hogan RP 3rd, Schwenk GR Jr, Griep JA (1983) Multinucleate megakaryocytes in refractory anemia with excess blasts. Arch Pathol Lab Med 107:277–278PubMed Wheeler LA, Hogan RP 3rd, Schwenk GR Jr, Griep JA (1983) Multinucleate megakaryocytes in refractory anemia with excess blasts. Arch Pathol Lab Med 107:277–278PubMed
46.
go back to reference Wijermans PW, Krulder JW, Huijgens PC, Neve P (1997) Continuous infusion of low-dose 5-aza-2′-deoxycytidine in elderly patients with high-risk myelodysplastic syndrome. Leukemia 11:1–5CrossRefPubMed Wijermans PW, Krulder JW, Huijgens PC, Neve P (1997) Continuous infusion of low-dose 5-aza-2′-deoxycytidine in elderly patients with high-risk myelodysplastic syndrome. Leukemia 11:1–5CrossRefPubMed
47.
go back to reference Wijermans P, Lübbert M, Verhoef G, Bosly A, Ravoet C, Andre M, Ferrant A (2000) Low-dose 5-aza-2′-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients. J Clin Oncol 18:956–962PubMed Wijermans P, Lübbert M, Verhoef G, Bosly A, Ravoet C, Andre M, Ferrant A (2000) Low-dose 5-aza-2′-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients. J Clin Oncol 18:956–962PubMed
48.
go back to reference Wijermans PW, Lübbert M, Verhoef G, Klimek V, Bosly A (2005) An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2′-deoxycytidine (decitabine) in 177 patients. Ann Hematol. DOI 10.1007/s00277-005-0012-1 Wijermans PW, Lübbert M, Verhoef G, Klimek V, Bosly A (2005) An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2′-deoxycytidine (decitabine) in 177 patients. Ann Hematol. DOI 10.1007/s00277-005-0012-1
49.
go back to reference Zucker-Franklin D (2003) Megakaryocytes and platelets. In: Zucker-Franklin D, Grossi CE (eds) An atlas of blood cells, function and pathology, 3rd edn. Edi-Ermes, Milan Zucker-Franklin D (2003) Megakaryocytes and platelets. In: Zucker-Franklin D, Grossi CE (eds) An atlas of blood cells, function and pathology, 3rd edn. Edi-Ermes, Milan
Metadata
Title
The hematopathological basis for studying effects of the demethylating agent 5-aza-2′-deoxycytidine (decitabine) in myelodysplasia
Authors
Hans Eckart Schaefer
Michael Lübbert
Publication date
01-12-2005
Publisher
Springer-Verlag
Published in
Annals of Hematology / Issue Special Issue 1/2005
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-005-0034-8

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