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megarakaryoblastic leukemia (AMKL) associated with trisomy 21, and anemia associated with the production of GATA-1s. 45 GATA-1 has two zinc fingers essential for normal function. The C-terminal finger is necessary for DNA binding. The N-terminal finger mediates interaction with FOG-1, a cofactor for GATA-1. A family with X-linked dyserythropoietic anaemia and thrombocytopenia due to a substitution of methionine for valine at amino acid 205 of GATA-1 was described. 46 This highly conserved valine is necessary for interaction of the amino-terminal zinc finger of GATA-1 with its essential cofactor, FOG-1 (for friend of GATA-1). They showed that the V205M mutation abrogates the interaction between Gata-1 and Fog-1, inhibiting the ability of GATA-1 to rescue erythroid differentiation in an erythroid cell line deficient for GATA-1 (G1E). Their findings underscore the importance of FOG-1:GATA-1 associations in both megakaryocyte and erythroid development, and suggest that other X-linked anemias or thrombocytopenias may be caused by defects in GATA1. This mutation most closely resembles those of mice with the ‘knockdown’ Gata1 mutation. Another group described a family with a novel single base mutation that results in an amino acid substitution (Gly208Arg) within the highly conserved portion of the GATA-1 N-terminal finger domain, leading to dyserythropoietic anemia and macrothrombocytopenia. 47 In the 90s a 10-year-old female Danish case was extensively described. 48-51 She showed severe anemia at birth and required repeated transfusion during childhood. The clinical characteristic exhibited by the patient was persistent expression of ε and ζ embryonic globin, an HbF level of 40%, novel intra-erythroblastic and intra-erythrocytic inclusions and deficiency of erythroid proteins CD44 and Aquaporin 1. The marrow aspirate studies revealed active erythropoiesis with some dyserythropoietic features. Blood grouping tests further showed that the child has the very rare Co(a-b-) blood group phenotype and is negative for the high incidence antigen AnWj. 50 Only recently an erythroid transcriptional factor alteration has been elucidated. It was the case of two patients with a hitherto unclassified CDA in whom a missense mutation in KLF1 has been identified. One of these was a Danish patient previously described. The first patient described showed a similar clinical phenotype of Danish. KLF1 is an erythroid transcription factor, and extensive studies in mouse models have shown that it plays a critical role in the expression of globin genes, but also in the expression of a wide spectrum of genes potentially essential for erythropoiesis. 52-54 The unique features of this CDA confirm the key role of KLF1 during human erythroid differentiation. Sequencing of KLF1 in both patients revealed the presence of de novo c.973G>A (p.E325K) mutation that had never been reported and was not present in 96 regular blood, suggesting it was the disease-causing mutation. The authors suggested that mutations in KLF1 cause a hitherto unclassified CDA. 55 Finally, in recent months the case of a patient with mevalonate kinase deficiency (MKD) and congenital dyserythropoietic anemia has been described. The clinical phenotype was variable, ranging from the hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) to mevalonic aciduria (MA), a severe metabolic disease. Genomic sequencing of the mevalonate kinase gene revealed compound heterozygosity for a missense mutation previously described in MA (V310M) and a novel missense mutation (Y116H). In contrast, sequencing of SEC23B gene revealed no mutations, suggesting that the bone marrow abnormalities were causally related to the MKD. 56 References London, United Kingdom, June 9-12, 2011 1. Renella R, Wood WG. The congenital dyserythropoietic anemias. Hematol Oncol Clin North Am. 2009; 23:283-306. 2. Iolascon A, Russo R and Delaunay J. Congenital dyserythrpoietic anemias. Curr. Op. Hematol. 2011; (May), in press. 3. Heimpel H, Wendt F. Congenital dyserythropoietic anemia with karyorhexis and multinuclearity of erythroblasts. Helv Med Acta. 1968;34:103-112. 4. Crookston JH, Crookston MC, Burnie KL, Francombe WH, Dacie JV, Lewis SM. Hereditary erythroblastic multinuclearity associated with a positive acidified-serum test: a type of congenital dyserythropoietic anaemia. Br J Haematol. 1969;17:11-23. 5. Heimpel H, Matuschek A, Ahmed M, Bader-Meunier B, Colita A, Delaunay J et al. Frequency of congenital dyserythropoietic anemias in Europe. Eur J Haematol. 2010;85:20-5. 6. Heimpel H, Schwarz K, Ebnöther M, Goede JS, Heydrich D, Kamp T et al. Congenital dyserythropoietic anemia type I (CDA I): molecular genetics, clinical appearance, and prognosis based on long-term observation. Blood. 2006;107:334-40. 7. Iolascon A, Delaunay J. Close to unraveling the secrets of congenital dyserythropoietic anemia types I and II. Haematologica. 2009;94:599-602. 8. Heimpel H, Kellermann K, Neuschwander N, Högel J, Schwarz K. The morphological diagnosis of congenital dyserythropoietic anemia: results of a quantitative analysis of peripheral blood and bone marrow cells. Haematologica. 2010; 95:1034-6. 9. Dgany O, Avidan N, Delaunay J, Krasnov T, Shalmon L, Shalev H et al. Congenital dyserythropoietic anemia type I (CDAN1) is caused by mutations in codanin-1. Am. J. Hum. Genet. 2000;71:1467-74. 10. Tamary H, Dgany O, Proust A, Krasnov T, Avidan N, Eidelitz- Markus T et al. Clinical and molecular variability in congenital dyserythropoietic anemia type I. Br J Haematol. 2005;130:628-34. 11. Ahmed MR, Chehal A, Zahed L, Taher A, Haidar J, Shamseddine A et al. Linkage and mutational analysis of the CDAN1 gene reveals genetic heterogeneity in congenital dyserythropoietic anemia type I. Blood. 2006;107:4968-9. 12. Noy-Lotan S, Dgany O, Lahmi R, Marcoux N, Krasnov T, Yissachar N et al. Codanin-1, the protein encoded by the gene mutated in congenital dyserythropoietic anemia type I (CDAN1), is cell cycle-regulated. Haematol. 2009;94:629-37. 13. Tamary H, Marcoux N, Noy-Lotan S, Yaniv I and Dgany O. Codanin 1, the product of the gene mutated in congenital dyserythropoietic anemia type I (CDAN1), binds to histone chaperone Asf1a and inhibits its nucleasome assembly activity. Blood. ASH abstract book 2010 n°1004. 14. Renella R, Roberts N, Brown JM, De Gobbi M, Bird L, Hassanali T et al. Codanin-1 mutations in congenital dyserythropoietic anemia type I affect HP1-alpha localization in erythroblasts. Blood. 2011 March (Epub ahead of print). 15. Goede JS, Benz R, Fehr J, Schwarz K, Heimpel H. Congenital dyserythropoietic anemia type I with bone abnormalities, mutations of the CDAN 1 gene and significant responsiveness to alpha-interferon therapy. Ann Hematol. 2006;85:591-5. 16. Tamary H, Shalev H, Perez-Avraham G, Zoldan M, Levi I, Swinkels DW et al. Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I. Blood. 2008;112:5241-4. 17. Heimpel H, Anselstetter V, Chrobak L, Denecke J, Einsiedler B, Gallmeier K et al. Congenital dyserythropoietic anemia type II: epidemiology, clinical appearance, and prognosis based on long-term observation. Blood. 2003;102:4576-5581. 18. Iolascon A, D’Agostaro G, Perrotta S, Izzo P, Tavano R, Miraglia del Giudice B. Congenital dyserythropoietic anemia type II: molecular basis and clinical aspects. Haematologica. 1996;81:543-59. 19. Perrotta S, Del Giudice EM, Carbone R, Servedio V, Schettini F Jr, Nobili B et al. Gilbert’s syndrome accounts for the pheno- Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1) | 321 |
16 th Congress of the European Hematology Association typic variability of congenital dyserythropoietic anemia type II (CDA II). J Pediatr. 2000;136:556-9. 20. Bird AR, Jacobs P, Moores P. Congenital dyserythropoietic anaemia (type II) presenting with haemosiderosis. Acta Haematol. 1987;78:33-6. 21. Lugassy G, Michaeli J, Harats N, Libson E, Rachmilewitz EA. Paravertebral extramedullary hematopoiesis associated with improvement of anemia in congenital dyserythropoietic anemia type II. Am J Hematol. 1986;22:295-300. 22. Hines GL. Paravertebral extramedullary hematopoiesis (as a posterior mediastinal tumor) associated with congenital dyserythropoietic anemia. J Thorac Cardiovasc Surg. 1993;106:760-1. 23. Imran A, Mawhinney R, Swirsky D, Hall C. Paravertebral extramedullary haemopoiesis occurring in a case of congenital dyserythropoietic anaemia type II. Br J Haematol. 2008;140:1. 24. Steiner W, Denzlinger C, Weiss M. Paravertebral extramedullary hematopoiesis in congenital dyserythropoietic anemia type II (CDA II). Rontgenpraxis. 1995;48:110-2. 25. Halpern Z, Rahmani R, Levo Y. Severe hemochromatosis: the predominant clinical manifestation of congenital dyserythropoietic anemia type 2. Acta Haematol. 1985;74:178-80. 26. Tamura H, Matsumoto G, Itakura Y, Terai H, Ikebuchi K, Mitarai T et al. A case of congenital dyserythropoietic anemia type II associated with hemochromatosis. Intern Med. 1992; 31:380-4. 27. Verwilghen RL, Lewis SM, Dacie JV, Crookston JH, Crookston MC. HEMPAS: congenital dyserythropoietic anaemia (type II). Q J Med. 1973;42:257-78. 28. Breton-Gorius J, Daniel MT, Clauvel JP, Dreyfus B. [Ultrastructural abnormalities of erythroblasts and erythrocytes in 6 cases of congenital dyserythropoietic anemia]. Nouv Rev Fr Hematol. 1973;13:23-49. 29. Verwilghen RL, Tan P, De Wolf-Peeters C, Broeckaert-van Orshoven, Louwagie AC. Cell membrane anomaly impeding cell division. Experientia. 1971;27:1467-8. 30. Wong KY, Hug G, Lampkin BC. Congenital dyserythropoietic anemia type II: ultrastructural and radioautographic studies of blood and bone marrow. Blood. 1972;39:23-30. 31. Alloisio N, Texier P, Denoroy L, Berger C, Miraglia del Giudice E, Perrotta S et al. The cisternae decorating the red blood cell membrane in congenital dyserythropoietic anemia (type II) originate from the endoplasmic reticulum. Blood. 1996;87: 4433-9. 32. Mawby WJ, Tanner MJ, Anstee DJ, Clamp JR. Incomplete glycosylation of erythrocyte membrane proteins in congenital dyserythropoietic anaemia type II (CDA II). Br J Haematol. 1983;55:357-68. 33. Baines AJ, Banga JP, Gratzer WB, Linch DC, Huehns ER. Red cell membrane protein anomalies in congenital dyserythropoietic anaemia, type II (HEMPAS). Br J Haematol. 1982; 50:563-74. 34. Scartezzini P, Forni GL, Baldi M, Izzo C, Sansone G. Decreased glycosylation of band 3 and band 4.5 glycoproteins of erythrocyte membrane in congenital dyserythropoietic anaemia type II. Br J Haematol. 1982;51:569-76. 35. Tomita A, Parker CJ. Aberrant regulation of complement by the erythrocytes of hereditary erythroblastic multinuclearity with a positive acidified serum lysis test (HEMPAS). Blood. 1994;83:250-9. 36. Gasparini P, Miraglia del Giudice E, Delaunay J, Totaro A, Granatiero M, Melchionda S et al. Localization of the congenital dyserythropoietic anemia II locus to chromosome 20q11.2 by genome wide search. Am J Hum Genet. 1997;61:1112-6. 37. Schwarz K, Iolascon A, Verissimo F, Trede NS, Horsley W, Chen W et al. Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II. Nat Genet. 2009;41:936-40. 38. Lee MC, Miller EA, Goldberg J, Orci L, Schekman R. Bi-directional protein transport between the ER and Golgi. Annu. Rev. Cell Dev. Biol. 2004; 20:87-123. 39. Fromme JC, Orci L, Schekman R. Coordination of COPII vesicle trafficking by Sec23. Trends Cell Biol. 2008; 18:330-336. 40. Jones B, Jones EL, Bonney SA, Patel HN, Mensenkamp AR, Eichenbaum-Voline S et al. Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders. Nat Genet. 2003;34:29-31. 41. Boyadjiev SA, Fromme JC, Ben J, Chong SS, Nauta C, Hur DJ et al. Cranio-lenticulo-sutural dysplasia is caused by a SEC23A mutation leading to abnormal endoplasmic-reticulum-to- Golgi trafficking. Nat Genet. 2006;38:1192-7. 42. Iolascon A, Russo R, Esposito MR, Asci R, Piscopo C, Perrotta S et al. Molecular analysis of 42 patients with congenital dyserythropoietic anemia type II: new mutations in the SEC23B gene and a search for a genotype-phenotype relationship. Haematologica. 2010;95:708-15. 43. Russo R, Esposito MR, Asci R, Gambale A, Perrotta S, Ramenghi U et al. Mutational spectrum in congenital dyserythropoietic anemia type II: identification of 19 novel variants in SEC23B gene. Am J Hematol. 2010; 85:915-20. 44. Vasievich M, Zhang B, Rinehart J, Jones M, Maillard I, Ginsburg D et al. Sec23b deficiency in mice results in pancreatic desctruction and defective long term hemopoietic stem cell function. Blood. ASH abstract blook 2010 n° 2038. 45. Ciovacco WA, Raskind WH, Kacena MA. Human phenotypes associated with GATA-1 mutations. Gene. 2008;427:1-6. Epub 2008 Sep 30. 46. Nichols KE, Crispino JD, Poncz M, White JG, Orkin SH, Maris JM et al. Familial dyserythropoietic anaemia and thrombocytopenia due to an inherited mutation in GATA1. Nat Genet. 2000;24:266-70. 47. Del Vecchio GC, Giordani L, De Santis A, De Mattia D. Dyserythropoietic anemia and thrombocytopenia due to a novel mutation in GATA-1. Acta Haematol. 2005;114:113-6. 48. Wickramasinghe SN, Illum N, Wimberley PD. Congenital dyserythropoietic anaemia with novel intra-erythroblastic and intra-erythrocytic inclusions. Br J Haematol. 1991;79:322-30. 49. Tang W, Cai SP, Eng B, Poon MC, Waye JS, Illum N et al. Expression of embryonic zeta-globin and epsilon-globin chains in a 10-year-old girl with congenital anemia. Blood. 1993;81:1636-40. 50. Parsons SF, Jones J, Anstee DJ, Judson PA, Gardner B, Wiener E et al. A novel form of congenital dyserythropoietic anemia associated with deficiency of erythroid CD44 and a unique blood group phenotype [In(a-b-), Co(a-b-)]. Blood. 1994; 83:860-8. 51. Agre P, Smith BL, Baumgarten R, Preston GM, Pressman E, Wilson P et al. Human red cell Aquaporin CHIP. II. Expression during normal fetal development and in a novel form of congenital dyserythropoietic anemia. J Clin Invest. 1994;94:1050-8. 52. Nuez B, Michalovich D, Bygrave A, Ploemacher R, Grosveld F. Defective haematopoiesis in fetal liver resulting from inactivation of the EKLF gene. Nature. 1995;375:316-8. 53. Perkins AC, Sharpe AH, Orkin SH. Lethal beta-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF. Nature. 1995;375:318-22. 54. Drissen R, von Lindern M, Kolbus A, Driegen S, Steinlein P, Beug H. The erythroid phenotype of EKLF-null mice: defects in hemoglobin metabolism and membrane stability. Mol Cell Biol. 2005;25:5205-14. 55. Arnaud L, Saison C, Helias V, Lucien N, Steschenko D, Giarratana MC et al. A dominant mutation in the gene encoding the erythroid transcription factor KLF1 causes a congenital dyserythropoietic anemia. Am J Hum Genet. 2010;87:721-7. Epub 2010 Nov 4. 56. Samkari A, Borzutzky A, Fermo E, Treaba DO, Dedeoglu F, Altura RA. A novel missense mutation in MVK associated with MK deficiency and dyserythropoietic anemia. Pediatrics. 2010;125:e964-8. Epub 2010 Mar 1. | 322 | Hematology Education: the education programme for the annual congress of the European Hematology Association | 2011; 5(1)
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H e m a t o l o g y E d u c a t i o
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Copyright Information ©2011 by Eur
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Editorial Board Education Book Edit
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Acute lymphoblastic leukemia 1-8 Th
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S. Schnell P. Van Vlierberghe A. Fe
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lineage cells, and in differentiati
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FLT3 mutations The FMS-like tyrosin
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44. Bar-Eli M, Ahuja H, Foti A, Cli
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J.M. Rowe 1,2 C. Ganzel 1 1 Shaare
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treated on the MRC UKALL XII/ECOG29
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asparaginase (PEG), where the Esche
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or higher. It is, however, importan
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25. Bruggemann M, Schrauder A, Raff
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lymphoblastic leukemia: prospective
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such as high white blood cell count
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doxorubicine, there was a trend tow
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of the aging process with respect t
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K.L. Rice 1 M. Buzzai 2 J. Altman 1
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ing FLT3-ITD, wild-type NPM1, or bo
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ciated with gene activation, via th
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leukemia with inv(16) and t(8;21):
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99. Parsons DW, Jones S, Zhang X, e
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abnormalities, some of which are al
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file. 27,31 Thus, the double gene-m
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karyotype represents a distinct gen
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Table 1. Meta-analysis of 23 random
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A recent study by the Center for In
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Patients with HLA-matched related o
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After allogeneic HSCT, an autologou
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A. Bacigalupo Ospedale San Martino,
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Table 2. The effect of HLA mismatch
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References 1. Petersdorf EW, Malkki
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neutrophil and platelet recovery an
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Figure 2. One Year-Overall Survival
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infused on day 21. No serious adver
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W, et al. Effect of graft source on
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TRM was higher for patients who rec
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following a myeloablative preparati
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effect. Surprisingly, none of the p
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nancies. Bone Marrow Transplant. 20
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J.G. Gilles Center for Molecular an
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14C12 was humanized by grafting VH
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Table 1. VWD Classification. VWD Su
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Figure 1. Missense mutations found
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associated with an increased bleedi
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49. Brown SA, Eldridge A, Collins P
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leed. These issues are especially i
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estored function. 43,44 A phase I t
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years’ experience of prophylactic
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J.A. Burger Department of Leukemia,
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chemotaxis, migration across vascul
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Regulatory T cells (T reg), identif
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16. Burger JA, Ghia P, Rosenwald A,
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TE, Nowakowski GS, et al. CD49d exp
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andomized trial demonstrating impro
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Conclusions Chemoimmunotherapy has
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with multiple comorbidities (≥ 2)
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ment was finished in all 100 patien
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Table 2. Treatment recommendation f
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34. Ferrajoli A. The combination of
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to be the source of additional gene
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potential to prevent LSCs from acce
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ABL1 confirms that eradication of d
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65. Fiskus W, Pranpat M, Balasis M,
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alive after 10 years. 11 Hence, CCy
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each arm). A minimal change in myel
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Any discussion about the definition
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H. Kantarjian J. Cortes Leukemia De
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59%; the CCyR rate was 44%. Among p
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ern era of BCR-ABL1 tyrosine kinase
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the hematopoietic system, 10 nor in
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over the period of 6 weeks, demonst
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Data on clonal changes in the blood
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2006 Feb 1;107(3):924-30. 41. Liang
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demonstrated that changes in osteob
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“Mafia” transgenic mice in whic
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68. Coetzee T, Fujita N, Dupree J,
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ization. In WASP deficiency, lympho
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Currently the epistatic relationshi
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R. Küppers Institute of Cell Biolo
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Figure 1. TNFAIP3 mutation in HL ce
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Figure 2. HRS cells and their precu
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Hansmann ML, et al. Detection of cl
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fying patients for whom different a
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prognosis HL, whilst those with res
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12. Noordijk EM, Carde P, Dupouy N,
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A. Sureda Consultant in Haematology
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Figure 1. Long-term outcome of pati
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from a MRD and 18 from MUDs. All pa
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Parker PM, Stein AS, et al. High-do
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R. Stasi Department of Haematology,
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common variants in the regulatory r
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against the TPO receptor (cMpl). 61
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W.B. Mitchell A.A. Miller J.B. Buss
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platelet counts and/or bleeding. Th
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Mpl. Cell. 1994;77(7):1117-24. 6. d
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ity and mortality associated with t
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to azathioprine, and is particularl
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stemming from antibodies against PE
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L. Pasqualucci Institute for Cancer
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cation of molecularly distinct subg
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of cases) 46 and amplifications of
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gene alterations in B cell lymphoma
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W. Wilson National Cancer Institute
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clear distinction among the lymphom
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Treatment strategies in germinal ce
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in ABC DLBCL (Hernandez et al., 201
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DLBCL that mostly occurs in young p
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phoma. J Clin Oncol. 2005;23:5347-5
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Table 1. Diffuse Large B cell Lymph
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sion/relapse are similar to those i
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intensive therapy with curative int
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A. Karsan Genome Sciences Centre an
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Balanced translocations In contrast
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some arm 5q have also been implicat
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(H3K27) methyltransferase, and is a
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38. Starczynowski DT, Morin R, McPh
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G. Garcia-Manero Department of Leuk
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trial evaluating different doses an
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acid. 62 The second was a large mul
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Borthakur G, et al. Cause of death
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P. Krishnamurthy 1 G.J. Mufti 1,2 1
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etween 1995 and 2005. 11 Five hundr
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London, United Kingdom, June 9-12,
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attainment of FDC post DLI. Interes
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myelodysplastic syndromes is associ
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ubiquitous chaperone that promotes
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was thought that they are linked to
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pathologic induction of miR-28 in M
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STATs. Second, levels of HP1 alpha
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72. Irandoust MI, Aarts LH, Roovers
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A.M. Vannucchi Section of Hematolog
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2,559 patients with a diagnosis of
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tant use of aspirin should be caref
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sions at this regard. Based on thes
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in bcr-abl-negative myeloproliferat
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Table 1. Prognostic scoring systems
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Figure 1. Current inhibitors of JAK
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Table 4. A risk-based approach to d
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Page 286 and 287: Mevastatin, a specific inhibitor of
Page 288 and 289: egression of tumor vessels, and app
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Page 296 and 297: Table 1. Conventional chemotherapy
Page 298 and 299: Novel agents given as consolidation
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Page 302 and 303: 31. Barlogie B, Tricot G, Anaissie
Page 304 and 305: Table 1. Major differences between
Page 306 and 307: first line therapy have shown survi
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Page 312 and 313: Table 1. Clinical signs of possible
Page 314 and 315: Table 4. Distribution of CSF involv
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Page 318 and 319: 90. German-Austrian-Swiss ALL-BFM S
Page 320 and 321: U. Nowak-Göttl 1 R. Junker 1 A. Kr
Page 322 and 323: Based on the data obtained from the
Page 324 and 325: 59. Male C, Chait P, Ginsberg JS, e
Page 326 and 327: Table 1. Characteristic features of
Page 328 and 329: Table 2. Mutational spectrum of CDA
Page 332 and 333: R.E. Ware Professor and Vice-Chairm
Page 334 and 335: protein, cytokines, and soluble adh
Page 336 and 337: example, improving blood viscosity
Page 338 and 339: 92(9):1266-7. 36. Bensinger TA, Gil
Page 340 and 341: London, United Kingdom, June 9-12,
Page 342 and 343: port have also been used. 5 Combina
Page 344 and 345: Wingard JR, Young J-AH, Boeckh MJ.
Page 346 and 347: K. Rezvani 1 J. Barrett 2 1 Haemato
Page 348 and 349: include the childhood infectious il
Page 350 and 351: Summary Patients undergoing hematop
Page 352 and 353: Table 1. Key issues. In a retrospec
Page 354 and 355: invasive method to assess iron over
Page 356 and 357: stitution but even with optimal sub
Page 358 and 359: T.M. Hackeng Department of Biochemi
Page 360 and 361: and inhibits FVIIa, and that the se
Page 362 and 363: Figure 4. Regulation of coagulation
Page 364 and 365: T. Baglin Department of Haematology
Page 366 and 367: Figure 1. Illustration of alternati
Page 368 and 369: compared with 3.5% in patients with
Page 370 and 371: 49. Hron G, Kollars M, Binder BR, E
Page 372 and 373: Women receiving vitamin K antagonis
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Page 376 and 377: eral morbidity and mortality. 17-21
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Goals of future murine studies incl
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F. Noizat-Pirenne C. Tournamille Et
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phenotype. 26 In 2010, we investiga
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ody has been involved in DHTR. 37 T
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antigen. Cases can be encountered d
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S.R. Sloan Harvard Medical School &
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We also analyzed patient databases
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Index of authors Altman J. 27 Bacig
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Cornelissen J. Affiliations to disc
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GlaxoSmithKline (Research Support;
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