The Challenging world of cytopenias: Distinguishing myelodysplastic syndromes from other disorders of marrow failure

Oncologist

Volumn 19, Issue 7, 2014, Pages 735-745

  DeZern, Amy E ^a,b   Sekeres, Mikkael A ^c  

^a JOHNS HOPKINS UNIVERSITY   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c TAUSSIG CANCER INSTITUTE   (United States)

Author keywords

Aplastic anemia; Bone marrow failure; Large granular leukemia; Molecularmarkers; Myelodysplastic syndrome; PNH; SNP array

Indexed keywords

CD34 ANTIGEN; CD45 ANTIGEN; CD71 ANTIGEN; DNA METHYLTRANSFERASE 3A; FANCONI ANEMIA PROTEIN; JANUS KINASE 2; NUCLEOPHOSMIN; PROTEIN P53; STAT3 PROTEIN; TRANSCRIPTION FACTOR;

APLASTIC ANEMIA; BLACKFAN DIAMOND ANEMIA; BONE MARROW BIOPSY; BONE MARROW DEPRESSION; CD3+ T LYMPHOCYTE; DOWN REGULATION; DYSKERATOSIS CONGENITA; FLOW CYTOMETRY; FLUORESCENCE IN SITU HYBRIDIZATION; GENETIC SCREENING; HEMATOPOIESIS; HUMAN; IMMUNOHISTOCHEMISTRY; IMMUNOPHENOTYPING; IMMUNOSUPPRESSIVE TREATMENT; KARYOTYPING; LARGE GRANULAR LYMPHOCYTE LEUKEMIA; MYELODYSPLASTIC SYNDROME; MYELOFIBROSIS; OVERALL SURVIVAL; PAROXYSMAL NOCTURNAL HEMOGLOBINURIA; PRIORITY JOURNAL; PURE RED CELL ANEMIA; REFRACTORY ANEMIA WITH RINGED SIDEROBLASTS; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SOMATIC MUTATION; UPREGULATION; BLOOD; BONE MARROW DISEASES; DIFFERENTIAL DIAGNOSIS; MYELODYSPLASTIC SYNDROMES; PROGNOSIS;

BONE MARROW DISEASES; DIAGNOSIS, DIFFERENTIAL; HUMANS; MYELODYSPLASTIC SYNDROMES; PROGNOSIS;

EID: 84903578246     PISSN: 10837159     EISSN: 1549490X     Source Type: Journal    
DOI: 10.1634/theoncologist.2014-0056     Document Type: Review

References (110)

1. Young NS. Acquired Bone Marrow Failure. Philadelphia, PA: JB Lippincott, 1995.
2. Alter BP. Diagnosis, genetics, and management of inherited bone marrow failure syndromes. Hematology Am Soc Hematol Educ Program 2007; 29-39.
3. Tefferi A, Vardiman JW. Myelodysplastic syndromes. N Engl JMed 2009;361:1872-1885.
4. Whitman SP, Archer KJ, Feng L et al. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: A Cancer and Leukemia Group B study. Cancer Res 2001;61:7233-7239.
5. Malcovati L, Papaemmanuil E, Bowen DT et al. Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/ myeloproliferative neoplasms. Blood 2011;118: 6239-6246.
6. Malcovati L, Hellström-Lindberg E, Bowen D et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: Recommendations from the European LeukemiaNet. Blood 2013;122: 2943-2964.
7. Swerdlow SH, Campo E, Harris NL et al. WHO Classification ofTumoursof the Haematopoietic and Lymphoid Tissues. Lyon, France: International Agency for Research on Cancer, 2008.
8. Haase D, Germing U, Schanz J et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: Evidence from a core dataset of 2124 patients. Blood 2007;110: 4385-4395.
9. Solé F, Luño E, Sanzo C et al. Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes. Haematologica 2005; 90:1168-1178.
10. Schanz J, Steidl C, Fonatsch C et al. Coalesced multicentric analysis of 2,351 patients with myelodysplastic syndromes indicates an underestimation of poor-risk cytogenetics of myelodysplastic syndromes in the International Prognostic Scoring System. J Clin Oncol 2011;29:1963-1970.
11. Naqvi K, Jabbour E, Bueso-Ramos C et al. Implications of discrepancy in morphologic diagnosis of myelodysplastic syndrome between referral and tertiary care centers. Blood 2011;118: 4690-4693.
12. Leung W, Chen AR, Klann RC et al. Frequent detection of tumor cells in hematopoietic grafts in neuroblastoma and Ewing's sarcoma. Bone Marrow Transplant 1998;22:971-979.
13. Stetler-Stevenson M, Arthur DC, Jabbour N et al. Diagnostic utility of flow cytometric immunophenotyping in myelodysplastic syndrome. Blood 2001;98:979-987.
14. Matsui WH, Brodsky RA, Smith BD et al. Quantitative analysis of bone marrow CD34 cells in aplastic anemia and hypoplastic myelodysplastic syndromes. Leukemia 2006;20:458-462.
15. Malcovati L, Della Porta MG, Lunghi M et al. Flow cytometry evaluation of erythroid andmyeloid dysplasia in patients with myelodysplastic syndrome. Leukemia 2005;19:776-783.
16. Ogata K, Kishikawa Y, Satoh C et al. Diagnostic application of flow cytometric characteristics of CD341 cells in low-grade myelodysplastic syndromes. Blood 2006;108:1037-1044.
17. van de Loosdrecht AA, Ireland R, KernWet al. Rationale for the clinical application of flow cytometry in patients with myelodysplastic syndromes: Position paper of an international consortium and the European LeukemiaNet Working Group. Leuk Lymphoma 2013;54:472-475.
18. van de Loosdrecht AA, Westers TM, Westra AH et al. Identification of distinct prognostic subgroups in low-and intermediate-1-risk myelodysplastic syndromes by flow cytometry. Blood 2008;111: 1067-1077.
19. Maciejewski JP, Mufti GJ. Whole genome scanning as a cytogenetic tool in hematologic malignancies. Blood 2008;112:965-974.
20. Bejar R, Stevenson K, Abdel-Wahab O et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 2011;364:2496-2506.
21. Tiu RV, Gondek LP, O'Keefe CL et al. Prognostic impact of SNP array karyotyping in myelodysplastic syndromesand relatedmyeloid malignancies. Blood 2011;117:4552-4560.
22. Camitta BM, Thomas ED, Nathan DG et al. Severe aplastic anemia: A prospective study of the effect of early marrow transplantation on acute mortality. Blood 1976;48:63-70.
23. Borowitz MJ, Craig FE, Digiuseppe JA et al. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry B Clin Cytom 2010;78:211-230.
24. Parker C, Omine M, Richards S et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005;106:3699-3709.
25. Pu JJ, Hu R, Mukhina GL et al. The small population of PIG-A mutant cells in myelodysplastic syndromes do not arise from multipotent hematopoietic stem cells. Haematologica 2012;97: 1225-1233.
26. Brodsky RA, Mukhina GL, Li S et al. Improved detection and characterization of paroxysmal nocturnal hemoglobinuria using fluorescent aerolysin. Am J Clin Pathol 2000;114:459-466.
27. Sugimori C, Chuhjo T, Feng X et al. Minor population of CD55-CD59-blood cells predicts response to immunosuppressive therapy and prognosis in patients with aplastic anemia. Blood 2006; 107:1308-1314.
28. Sloand EM, Wu CO, Greenberg P et al. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol 2008;26:2505-2511.
29. Greenberg PL, Attar E, Bennett JM et al. Myelodysplastic syndromes: Clinical practice guidelines in oncology. J Natl Compr Canc Netw 2013;11: 838-874.
30. Lamy T, Loughran TP Jr. How I treat LGL leukemia. Blood 2011;117:2764-2774.
31. Koskela HL, Eldfors S, Ellonen P et al. Somatic STAT3 mutations in large granular lymphocytic leukemia. N Engl J Med 2012;366:1905-1913.
32. Walter MJ, Shen D, Shao J et al. Clonal diversity of recurrently mutated genes in myelodysplastic syndromes. Leukemia 2013;27:1275-1282.
33. Walter MJ, Shen D, Ding L et al. Clonal architecture of secondary acute myeloid leukemia. N Engl J Med 2012;366:1090-1098.
34. Heller PG, Glembotsky AC, Gandhi MJ et al. Low Mpl receptor expression in a pedigree with familial platelet disorder with predisposition to acute myelogenous leukemia and a novel AML1 mutation. Blood 2005;105:4664-4670.
35. Gaitonde S, Boumendjel R, Angeles R et al. Familial childhood monosomy 7 and associated myelodysplasia. J Pediatr Hematol Oncol 2010;32: e236-e237.
36. Alter BP. Fanconi's anemia, transplantation, and cancer. Pediatr Transplant 2005;9(suppl 7): 81-86.
37. Alter BP, Giri N, Savage SA et al. Malignancies and survival patterns in the National Cancer Institute inherited bone marrow failure syndromes cohort study. Br J Haematol 2010;150:179-188.
38. Alter BP, Giri N, Savage SA et al. Cancer in dyskeratosis congenita. Blood 2009;113:6549-6557.
39. Donadieu J, Fenneteau O, Beaupain B et al. Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome. Haematologica 2012;97:1312-1319.
40. Ballmaier M, Germeshausen M. Congenital amegakaryocytic thrombocytopenia: Clinical presentation, diagnosis, and treatment. Semin Thromb Hemost 2011;37:673-681.
41. Donadieu J, Leblanc T, Bader Meunier B et al. Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia. Haematologica 2005;90: 45-53.
42. Pasquet M, Bellanné-Chantelot C, Tavitian S et al. High frequency ofGATA2mutations in patients with mild chronic neutropenia evolving to Mono-Mac syndrome, myelodysplasia, and acute myeloid leukemia. Blood 2013;121:822-829.
43. Kazenwadel J, Secker GA, Liu YJ et al. Loss-offunction germlineGATA2mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature. Blood 2012;119:1283-1291.
44. Bejar R, Stevenson KE, Caughey BA et al. Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes. J Clin Oncol 2012;30:3376-3382.
45. Papaemmanuil E, Gerstung M, Malcovati L et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood 2013;122:3616-3627; quiz 3699.
46. Steensma DP, Gibbons RJ, Mesa RA et al. Somatic point mutations in RUNX1/CBFA2/AML1 arecommonin high-riskmyelodysplastic syndrome, but not in myelofibrosis with myeloid metaplasia. Eur J Haematol 2005;74:47-53.
47. Akagi T, Ogawa S, Dugas M et al. Frequent genomic abnormalities in acute myeloid leukemia/ myelodysplastic syndrome with normal karyotype. Haematologica 2009;94:213-223.
48. McNerney ME, BrownCD, Wang Xet al. CUX1is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia. Blood 2013;121:975-983.
49. Walter MJ, Ding L, Shen D et al. Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia 2011;25:1153-1158.
50. Tefferi A, Pardanani A, Lim KH et al. TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia 2009;23:905-911.
51. Delhommeau F, Dupont S, Della Valle V et al. Mutation in TET2 in myeloid cancers. N Engl J Med 2009;360:2289-2301.
52. Thol F, Weissinger EM, Krauter J et al. IDH1 mutations in patients with myelodysplastic syndromes are associated with an unfavorable prognosis. Haematologica 2010;95:1668-1674.
53. Boultwood J, Perry J, Pellagatti A et al. Frequent mutation of the polycomb-associated gene ASXL1 in the myelodysplastic syndromes and in acute myeloid leukemia. Leukemia 2010;24: 1062-1065.
54. Ernst T, Chase AJ, Score J et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet 2010;42: 722-726.
55. Bacher U, Haferlach T, Kern W et al. A comparative study of molecular mutations in 381 patients with myelodysplastic syndrome and in 4130 patients with acute myeloid leukemia. Haematologica 2007;92:744-752.
56. Murphy DM, Bejar R, Stevenson K et al. NRAS mutations with low allele burden have independent prognostic significance for patients with lower risk myelodysplastic syndromes. Leukemia 2013;27: 2077-2081.
57. Yoshida K, Sanada M, Shiraishi Y et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011;478:64-69.
58. Papaemmanuil E, Cazzola M, Boultwood J et al. Somatic SF3B1 mutation inmyelodysplasia with ring sideroblasts. N Engl J Med 2011;365:1384-1395.
59. Thol F, Kade S, Schlarmann C et al. Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes. Blood 2012;119:3578-3584.
60. Visconte V, Rogers HJ, Singh J et al. SF3B1 haploinsufficiency leads to formation of ring sideroblasts in myelodysplastic syndromes. Blood 2012; 120:3173-3186.
61. Shimamura A, Alter BP. Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev 2010;24:101-122.
62. Tsangaris E, Klaassen R, Fernandez CV et al. Genetic analysis of inherited bone marrow failure syndromes from one prospective, comprehensive and population-based cohort and identification of novel mutations. J Med Genet 2011;48:618-628.
63. Dezern AE, SymonsHJ, Resar LS et al. Detection of paroxysmal nocturnal hemoglobinuria clones to exclude inherited bone marrow failure syndromes. Eur J Haematol 2014;92:467-470.
64. Vulliamy TJ, Walne A, Baskaradas A et al. Mutations in the reverse transcriptase component of telomerase (TERT) in patients with bone marrow failure. Blood Cells Mol Dis 2005;34:257-263.
65. Du HY, Pumbo E, Ivanovich J et al. TERC and TERT gene mutations in patients with bone marrow failure and the significance of telomere length measurements. Blood 2009;113:309-316.
66. Armanios M. Syndromes of telomere shortening. Annu Rev Genomics Hum Genet 2009;10: 45-61.
67. Calado RT, Cooper JN, Padilla-Nash HM et al. Short telomeres result in chromosomal instability in hematopoietic cells and precede malignant evolution in human aplastic anemia. Leukemia 2012;26: 700-707.
68. Scheinberg P, Cooper JN, Sloand EM et al. Association of telomere length of peripheral blood leukocytes with hematopoietic relapse, malignant transformation, and survival in severe aplastic anemia. JAMA 2010;304:1358-1364.
69. Gadalla SM, Cawthon R, Giri N et al. Telomere length in blood, buccal cells, and fibroblasts from patients with inherited bone marrow failure syndromes. Aging (Albany, NY) 2010;2:867-874.
70. Aubert G, Hills M, Lansdorp PM. Telomere length measurement-caveats and a critical assessment of the available technologies and tools. Mutat Res 2012;730:59-67.
71. Brümmendorf TH, Maciejewski JP, Mak J et al. Telomere length in leukocyte subpopulations of patients with aplastic anemia. Blood 2001;97: 895-900.
72. Calado RT, Young NS. Telomere diseases. NEngl JMed 2009;361:2353-2365.
73. Rollison DE, Epling-Burnette PK, Park JY et al. Telomere length in myelodysplastic syndromes. Leuk Lymphoma 2011;52:1528-1536.
74. Poloni A, Serrani F, Berardinelli E et al. Telomere length, c-myc and mad-1 expression could represent prognosis markers of myelodysplastic syndrome. Leuk Res 2013;37:1538-1544.
75. Barrett J, Saunthararajah Y, Molldrem J. Myelodysplastic syndrome and aplastic anemia: Distinct entities or diseases linked by a common pathophysiology? Semin Hematol 2000;37:15-29.
76. Bennett JM, Orazi A. Diagnostic criteria to distinguish hypocellular acute myeloid leukemia from hypocellular myelodysplastic syndromes and aplastic anemia: Recommendations for a standardized approach. Haematologica 2009;94:264-268.
77. DameshekW. Riddle:Whatdoaplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH) and "hypoplastic" leukemia have in common? Blood 1967;30:251-254.
78. Young NS. The problem of clonality in aplastic anemia: Dr Dameshek's riddle, restated. Blood 1992;79:1385-1392.
79. de PlanqueMM, van Krieken JH, Kluin-Nelemans HCet al. Bone marrowhistopathology of patientswith severe aplastic anaemia before treatment and at follow-up. Br J Haematol 1989;72:439-444.
80. Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl JMed 1997;336: 1365-1372.
81. Morgan R, Hecht F. Deletion of chromosome band 13q14: A primary event in preleukemia and leukemia. Cancer Genet Cytogenet 1985;18: 243-249.
82. Afable MG II, Wlodarski M, Makishima H et al. SNP array-based karyotyping: Differences and similarities between aplastic anemia and hypocellular myelodysplastic syndromes. Blood 2011;117: 6876-6884.
83. Leguit RJ, van den Tweel JG. The pathology of bone marrow failure. Histopathology 2010;57: 655-670.
84. Geissler K, Hinterberger W, Jäger U et al. Deficiency of pluripotent hemopoietic progenitor cells in myelodysplastic syndromes. Blut 1988;57: 45-49.
85. Geissler K, HinterbergerW, Bettelheim P et al. Colony growth characteristics in chronic myelomonocytic leukemia. Leuk Res 1988;12:373-377.
86. Oehler L, Foedinger M, Koeller M et al. Interleukin-10 inhibits spontaneous colonyforming unit-granulocyte-macrophage growth from human peripheral blood mononuclear cells by suppression of endogenous granulocytemacrophage colony-stimulating factor release. Blood 1997;89:1147-1153.
87. DeZern AE, Pu J, McDevitt MA et al. Burstforming unit-erythroid assays to distinguish cellular bone marrow failure disorders. Exp Hematol 2013; 41:808-816.
88. Charles RJ, Sabo KM, Kidd PG et al. The pathophysiology of pure red cell aplasia: Implications for therapy. Blood 1996;87:4831-4838.
89. Füreder W, Paulitsch-Buckingham A, Rabitsch W et al. Evaluation of treatment responses and colony-forming progenitor cells in 50 patients with aplastic anemia after immunosuppressive therapy or hematopoietic stem cell transplantation: A single-center experience. Wien Klin Wochenschr 2014;126:119-125.
90. Valent P. Low blood counts: Immune mediated, idiopathic, ormyelodysplasia. HematologyAm Soc Hematol Educ Program 2012;485-491.
91. Tennant GB, Jacobs A, Bailey-Wood R. Peripheral blood granulocyte-macrophage progenitors in patients with the myelodysplastic syndromes. Exp Hematol 1986;14:1063-1068.
92. Shih LY, Chiu WF, Lee CT. Diagnostic and prognostic values of in vitro culture growth patterns of marrow granulocyte-macrophage progenitors in patients with myelodysplastic syndrome. Leukemia 1991;5:1092-1098.
93. Sloand EM, Melenhorst JJ, Tucker ZC et al. T-cell immune responses to Wilms tumor 1 protein in myelodysplasia responsive to immunosuppressive therapy. Blood 2011;117:2691-2699.
94. Barrett AJ, Sloand E. Autoimmune mechanisms in the pathophysiology of myelodysplastic syndromes and their clinical relevance. Haematologica 2009;94:449-451.
95. Saunthararajah Y, Nakamura R, Nam JM et al. HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome. Blood 2002;100:1570-1574.
96. Kasahara S, Hara T, Itoh H et al. Hypoplastic myelodysplastic syndromes can be distinguished from acquired aplastic anaemia by bone marrow stem cell expression of the tumour necrosis factor receptor. Br J Haematol 2002;118:181-188.
97. Goyal R, Qawi H, Ali I et al. Biologic characteristics of patients with hypocellular myelodysplastic syndromes. Leuk Res 1999;23:357-364.
98. Dunn DE, Tanawattanacharoen P, Boccuni P et al. Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Ann Intern Med 1999;131:401-408.
99. Wang H, Chuhjo T, Yamazaki H et al. Relative increase of granulocytes with a paroxysmal nocturnal haemoglobinuria phenotype in aplastic anaemia patients: The high prevalence at diagnosis. Eur J Haematol 2001;66:200-205.
100. Wang H, Chuhjo T, Yasue S et al. Clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria-type cells in bone marrow failure syndrome. Blood 2002;100:3897-3902.
101. Nakao S, Sugimori C, Yamazaki H. Clinical significance of a small population of paroxysmal nocturnal hemoglobinuria-type cells in the management of bone marrow failure. Int J Hematol 2006;84:118-122.
102. Young NS, Abkowitz JL, Luzzatto L. New insights into the pathophysiology of acquired cytopenias. Hematology Am Soc Hematol Educ Program 2000;18-38.
103. Sloand E, Kim S, Maciejewski JP et al. Intracellular interferon-gamma in circulating and marrow T cells detected by flow cytometry and the response to immunosuppressive therapy in patients with aplastic anemia. Blood 2002;100: 1185-1191.
104. Jerez A, Clemente MJ, Makishima H et al. STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia. Blood 2012; 120:3048-3057.
105. Saunthararajah Y, Molldrem JL, RiveraMet al. Coincident myelodysplastic syndrome and T-cell large granular lymphocytic disease: Clinical and pathophysiological features. Br J Haematol 2001; 112:195-200.
106. Cazzola M, Rossi M, Malcovati L. Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms. Blood 2013;121: 260-269.
107. Greenberg P, Cox C, LeBeau MM et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997;89: 2079-2088.
108. Greenberg PL, Tuechler H, Schanz J et al. Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndromes. Blood 2012;120:2454-2465.
109. Kantarjian H, O'Brien S, Ravandi F et al. Proposal for a new risk model in myelodysplastic syndromethataccounts forevents notconsidered in the original International Prognostic Scoring System. Cancer 2008;113:1351-1361.
110. Malcovati L, Germing U, Kuendgen A et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 2007;25: 3503-3510.