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Myelodysplastic Syndromes (MDS): Comparison
Please note this is a comparison between Version 2 by Camila Xu and Version 1 by Elena Crisa.

Myelodysplastic syndromes (MDS) comprise a group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, one or more peripheral cytopenias, single or multilineage dysplasia in the bone marrow (BM), and an increased risk of progressing to acute myeloid leukemia (AML), occurring eventually in approximately 30% of the cases, more rapidly in higher risk patients.

  • genetic predisposition
  • myelodysplastic syndromes
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References

  1. Arber, D.A.; Orazi, A.; Hasserjian, R.; Thiele, J.; Borowitz, M.J.; Le Beau, M.M.; Bloomfield, C.D.; Cazzola, M.; Vardiman, J.W. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016, 127, 2391–2405.
  2. Greenberg, P.L.; Tuechler, H.; Schanz, J.; Sanz, G.; Garcia-Manero, G.; Solé, F.; Bennett, J.M.; Bowen, D.; Fenaux, P.; Dreyfus, F.; et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012, 120, 2454–2465.
  3. Jaiswal, S.; Fontanillas, P.; Flannick, J.; Manning, A.; Grauman, P.V.; Mar, B.G.; Lindsley, R.C.; Mermel, C.H.; Burtt, N.; Chavez, A.; et al. Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes. N. Eng. J. Med. 2014, 371, 2488–2498.
  4. Papaemmanuil, E.; Gerstung, M.; Malcovati, L.; Tauro, S.; Gundem, G.; Van Loo, P.; Yoon, C.J.; Ellis, P.; Wedge, D.C.; Pellagatti, A.; et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood 2013, 122, 3616–3627.
  5. Bejar, R. Implications of molecular genetic diversity in myelodysplastic syndromes. Curr. Opin. Hematol. 2017, 24, 73–78.
  6. Kennedy, J.A.; Ebert, B.L. Clinical Implications of Genetic Mutations in Myelodysplastic Syndrome; American Society of Clinical Oncology: Alexandria, VA, USA, 2017; Volume 35, pp. 968–974.
  7. Sekeres, M.A. Epidemiology, natural history, and practice patterns of patients with myelodysplastic syndromes in 2010. J. Natl. Compr. Cancer Netw. 2011, 9, 57–63.
  8. Ma, X.; Does, M.; Raza, A.; Mayne, S.T. Myelodysplastic syndromes: Incidence and survival in the United States. Cancer 2007, 109, 1536–1542.
  9. Neukirchen, J.; Schoonen, W.M.; Strupp, C.; Gattermann, N.; Aul, C.; Haas, R.; Germing, U. Incidence and prevalence of myelodysplastic syndromes: Data from the Düsseldorf MDS-registry. Leuk. Res. 2011, 35, 1591–1596.
  10. Locatelli, F.; Strahm, B. How I treat myelodysplastic syndromes of childhood. Blood 2018, 131, 1406–1414.
  11. Ghemlas, I.; Li, H.; Zlateska, B.; Klaassen, R.; Fernandez, C.V.; Yanofsky, R.A.; Wu, J.; Pastore, Y.; Silva, M.; Lipton, J.H.; et al. Improving diagnostic precision, care and syndrome definitions using comprehensive next-generation sequencing for the inherited bone marrow failure syndromes. J. Med. Genet. 2015, 52, 575–584.
  12. Peffault de Latour, R.; Peters, C.; Gibson, B.; Strahm, B.; Lankester, A.; de Heredia, C.D.; Longoni, D.; Fioredda, F.; Locatelli, F.; Yaniv, I.; et al. Recommendations on hematopoietic stem cell transplantation for inherited bone marrow failure syndromes. Bone Marrow Transplant. 2015, 50, 1168–1172.
  13. Keel, S.B.; Scott, A.; Sanchez-Bonilla, M.; Ho, P.A.; Gulsuner, S.; Pritchard, C.C.; Abkowitz, J.L.; King, M.C.; Walsh, T.; Shimamura, A. Genetic features of myelodysplastic syndrome and aplastic anemia in pediatric and young adult patients. Haematologica 2016, 101, 1343–1350.
  14. Savage, S.A.; Dufour, C. Classical inherited bone marrow failure syndromes with high risk for myelodysplastic syndrome and acute myelogenous leukemia. Semin. Hematol. 2017, 54, 105–114.
  15. Schwartz, J.R.; Ma, J.; Lamprecht, T.; Walsh, M.; Wang, S.; Bryant, V.; Song, G.; Wu, G.; Easton, J.; Kesserwan, C.; et al. The genomic landscape of pediatric myelodysplastic syndromes. Nat. Commun. 2017, 8, 1–9.
  16. Bluteau, O.; Sebert, M.; Leblanc, T.; De Latour, R.P.; Quentin, S.; Lainey, E.; Hernandez, L.; Dalle, J.H.; De Fontbrune, F.S.; Lengline, E.; et al. A landscape of germ line mutations in a cohort of inherited bone marrow failure patients. Blood 2018, 131, 717–732.
  17. Sebert, M.; Passet, M.; Raimbault, A.; Rahme, R.; Raffoux, E.; Sicre de Fontbrune, F.; Cerrano, M.; Quentin, S.; Vasquez, N.; Da Costa, M.; et al. Germline DDX41 mutations define a significant entity within adult MDS/AML patients. Blood 2019, 134, 1441–1444.
  18. Cerrudo, C.S.; Ghiringhelli, P.D.; Gomez, D.E. Protein universe containing a PUA RNA-binding domain. FEBS J. 2014, 281, 74–87.
  19. Keijzers, G.; Maynard, S.; Shamanna, R.A.; Rasmussen, L.J.; Croteau, D.L.; Bohr, V.A. The role of RecQ helicases in non-homologous end-joining. Crit. Rev. Biochem. Mol. Biol. 2014, 49, 463–472.
  20. Walne, A.J.; Marrone, A.; Dokal, I. Dyskeratosis congenita: A disorder of defective telomere maintenance? Int. J. Hematol. 2005, 82, 184–189.
  21. Otoshi, R.; Baba, T.; Shintani, R.; Kitamura, H.; Yamaguchi, Y.; Hamanoue, H.; Mizuguchi, T.; Matsumoto, N.; Okudela, K.; Takemura, T.; et al. Diverse pathological findings of interstitial lung disease in a patient with dyskeratosis congenita. Intern. Med. 2020.
  22. Alter, B.P.; Giri, N.; Savage, S.A.; Rosenberg, P.S. Cancer in the National Cancer Institute inherited bone marrow failure syndrome cohort after fifteen years of follow-up. Haematologica 2018, 103, 30–39.
  23. Bertuch, A.A. The molecular genetics of the telomere biology disorders. RNA Biol. 2016, 13, 696–706.
  24. Shimamura, A.; Alter, B.P. Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev. 2010, 24, 101–122.
  25. Alter, B.P. Fanconi anemia and the development of leukemia. Best Pract. Res. Clin. Haematol. 2014, 27, 214–221.
  26. Kelaidi, C.; Makis, A.; Petrikkos, L.; Antoniadi, K.; Selenti, N.; Tzotzola, V.; Ioannidou, E.D.; Tsitsikas, K.; Kitra, V.; Kalpini-Mavrou, A.; et al. Bone marrow failure in fanconi anemia: Clinical and genetic spectrum in a cohort of 20 pediatric patients. J. Pediatr. Hematol. Oncol. 2019, 41, 612–617.
  27. Alter, B.P.; Giri, N.; Savage, S.A.; Peters, J.A.; Loud, J.T.; Leathwood, L.; Carr, A.G.; Greene, M.H.; Rosenberg, P.S. Malignancies and survival patterns in the National Cancer Institute inherited bone marrow failure syndromes cohort study. Br. J. Haematol. 2010, 150, 179–188.
  28. Dong, H.; Nebert, D.W.; Bruford, E.A.; Thompson, D.C.; Joenje, H.; Vasiliou, V. Update of the human and mouse Fanconi anemia genes. Hum. Genom. 2015, 9, 32.
  29. Kennedy, A.L.; Shimamura, A. Genetic predisposition to MDS: Clinical features and clonal evolution. Blood 2019, 133, 1071–1085.
  30. McReynolds, L.J.; Calvo, K.R.; Holland, S.M. Germline GATA2 mutation and bone marrow failure. Hematol. Oncol. Clin. N. Am. 2018, 32, 713–728.
  31. Wlodarski, M.W.; Hirabayashi, S.; Pastor, V.; Starý, J.; Hasle, H.; Masetti, R.; Dworzak, M.; Schmugge, M.; van den Heuvel-Eibrink, M.; Ussowicz, M.; et al. Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents. Blood 2016, 127, 1387–1397.
  32. Bruzzese, A.; Leardini, D.; Masetti, R.; Strocchio, L.; Girardi, K.; Algeri, M.; Del Baldo, G.; Locatelli, F.; Mastronuzzi, A. GATA2 related conditions and predisposition to pediatric myelodysplastic syndromes. Cancers 2020, 12, 2962.
  33. Hsu, A.P.; Sampaio, E.P.; Khan, J.; Calvo, K.R.; Lemieux, J.E.; Patel, S.Y.; Frucht, D.M.; Vinh, D.C.; Auth, R.D.; Freeman, A.F.; et al. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood 2011, 118, 2653–2655.
  34. Hahn, C.N.; Chong, C.-E.; Carmichael, C.L.; Wilkins, E.J.; Brautigan, P.J.; Li, X.-C.; Babic, M.; Lin, M.; Carmagnac, A.; Lee, Y.K.; et al. Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. Nat. Genet. 2011, 43, 1012–1017.
  35. Ostergaard, P.; Simpson, M.A.; Connell, F.C.; Steward, C.G.; Brice, G.; Woollard, W.J.; Dafou, D.; Kilo, T.; Smithson, S.; Lunt, P.; et al. Mutations in GATA2 cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome). Nat. Genet. 2011, 43, 929–931.
  36. Burwick, N.; Shimamura, A.; Liu, J.M. Non-diamond blackfan anemia disorders of ribosome function: Shwachman Diamond syndrome and 5q- syndrome. Semin. Hematol. 2011, 48, 136–143.
  37. Austin, K.M.; Gupta, M.L., Jr.; Coats, S.A.; Tulpule, A.; Mostoslavsky, G.; Balazs, A.B.; Mulligan, R.C.; Daley, G.; Pellman, D.; Shimamura, A. Mitotic spindle destabilization and genomic instability in Shwachman-Diamond syndrome. J. Clin. Investig. 2008, 118, 1511–1518.
  38. Myers, K.C.; Bolyard, A.A.; Otto, B.; Wong, T.E.; Jones, A.T.; Harris, R.E.; Davies, S.M.; Dale, D.C.; Shimamura, A. Variable clinical presentation of Shwachman-Diamond syndrome: Update from the North American Shwachman-Diamond Syndrome Registry. J. Pediatr. 2014, 164, 866–870.
  39. Donadieu, J.; Fenneteau, O.; Beaupain, B.; Beaufils, S.; Bellanger, F.; Mahlaoui, N.; Lambilliotte, A.; Aladjidi, N.; Bertrand, Y.; Mialou, V.; 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. Davidsson, J.; Puschmann, A.; Tedgård, U.; Bryder, D.; Nilsson, L.; Cammenga, J. SAMD9 and SAMD9L in inherited predisposition to ataxia, pancytopenia, and myeloid malignancies. Leukemia 2018, 32, 1106–1115.
  41. Narumi, S.; Amano, N.; Ishii, T.; Katsumata, N.; Muroya, K.; Adachi, M.; Toyoshima, K.; Tanaka, Y.; Fukuzawa, R.; Miyako, K.; et al. SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7. Nat. Genet. 2016, 48, 792–797.
  42. Wong, J.C.; Bryant, V.; Lamprecht, T.; Ma, J.; Walsh, M.; Schwartz, J.; Del Pilar Alzamora, M.; Mullighan, C.G.; Loh, M.L.; Ribeiro, R.; et al. Germline SAMD9 and SAMD9L mutations are associated with extensive genetic evolution and diverse hematologic outcomes. JCI Insight 2018, 3, 1–12.
  43. Gorcenco, S.; Komulainen-Ebrahim, J.; Nordborg, K.; Suo-Palosaari, M.; Andréasson, S.; Krüger, J.; Nilsson, C.; Kjellström, U.; Rahikkala, E.; Turkiewicz, D.; et al. Ataxia-pancytopenia syndrome with SAMD9L mutations. Neurol. Genet. 2017, 3, 1–7.
  44. Tesi, B.; Davidsson, J.; Voss, M.; Rahikkala, E.; Holmes, T.D.; Chiang, S.C.C.; Komulainen-Ebrahim, J.; Gorcenco, S.; Nilsson, A.R.; Ripperger, T.; et al. Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms. Blood 2017, 129, 2266–2279.
  45. Galera, P.; Dulau-Florea, A.; Calvo, K.R. Inherited thrombocytopenia and platelet disorders with germline predisposition to myeloid neoplasia. Int. J. Lab. Hematol. 2019, 41, 131–141.
  46. Noris, P.; Pecci, A. Hereditary thrombocytopenias: A growing list of disorders. Hematology 2017, 2017, 385–399.
  47. Noetzli, L.; Lo, R.W.; Lee-Sherick, A.B.; Callaghan, M.; Noris, P.; Savoia, A.; Rajpurkar, M.; Jones, K.; Gowan, K.; Balduini, C.; et al. Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia. Nat. Genet. 2015, 47, 535–538.
  48. Melazzini, F.; Palombo, F.; Balduini, A.; De Rocco, D.; Marconi, C.; Noris, P.; Gnan, C.; Pippucci, T.; Bozzi, V.; Faleschini, M.; et al. Clinical and pathogenic features of ETV6-related thrombocytopenia with predisposition to acute lymphoblastic leukemia. Haematologica 2016, 101, 1333–1342.
  49. Aspesi, A.; Ellis, S.R. Rare ribosomopathies: Insights into mechanisms of cancer. Nat. Rev. Cancer 2019, 19, 228–238.
  50. Da Costa, L.; Narla, A.; Mohandas, N. An update on the pathogenesis and diagnosis of Diamond-Blackfan anemia. F1000Res 2018, 7.
  51. Vlachos, A.; Rosenberg, P.S.; Atsidaftos, E.; Alter, B.P.; Lipton, J.M. Incidence of neoplasia in Diamond Blackfan anemia: A report from the Diamond Blackfan Anemia Registry. Blood 2012, 119, 3815–3819.
  52. Welte, K.; Zeidler, C.; Dale, D.C. Severe Congenital Neutropenia. Semin. Hematol. 2006, 43, 189–195.
  53. Carlsson, G.; Fasth, A.; Berglöf, E.; Lagerstedt-Robinson, K.; Nordenskjöld, M.; Palmblad, J.; Henter, J.I.; Fadeel, B. Incidence of severe congenital neutropenia in Sweden and risk of evolution to myelodysplastic syndrome/leukaemia. Br. J. Haematol. 2012, 158, 363–369.
  54. Horwitz, M.S.; Duan, Z.; Korkmaz, B.; Lee, H.-H.; Mealiffe, M.E.; Salipante, S.J. Neutrophil elastase in cyclic and severe congenital neutropenia. Blood 2006, 109, 1817–1824.
  55. Lindsley, R.C.; Saber, W.; Mar, B.G.; Redd, R.; Wang, T.; Haagenson, M.D.; Grauman, P.V.; Hu, Z.H.; Spellman, S.R.; Lee, S.J.; et al. Prognostic mutations in myelodysplastic syndrome after stem-cell transplantation. N. Engl. J. Med. 2017, 376, 536–547.
  56. Maserati, E.; Pressato, B.; Valli, R.; Minelli, A.; Sainati, L.; Patitucci, F.; Marletta, C.; Mastronuzzi, A.; Poli, F.; Lo Curto, F.; et al. The route to development of myelodysplastic syndrome/acute myeloid leukaemia in Shwachman-Diamond syndrome: The role of ageing, karyotype instability, and acquired chromosome anomalies. Br. J. Haematol. 2009, 145, 190–197.
  57. Myers, K.C.; Furutani, E.; Weller, E.; Siegele, B.; Galvin, A.; Arsenault, V.; Alter, B.P.; Boulad, F.; Bueso-Ramos, C.; Burroughs, L.; et al. Clinical features and outcomes of patients with Shwachman-Diamond syndrome and myelodysplastic syndrome or acute myeloid leukaemia: A multicentre, retrospective, cohort study. Lancet. Haematol. 2020, 7, e238–e246.
  58. Chen, D.H.; Below, J.E.; Shimamura, A.; Keel, S.B.; Matsushita, M.; Wolff, J.; Sul, Y.; Bonkowski, E.; Castella, M.; Taniguchi, T.; et al. Ataxia-Pancytopenia Syndrome Is Caused by Missense Mutations in SAMD9L. Am. J. Hum. Genet. 2016, 98, 1146–1158.
  59. Honda, H.; Nagamachi, A.; Inaba, T. -7/7q- syndrome in myeloid-lineage hematopoietic malignancies: Attempts to understand this complex disease entity. Oncogene 2015, 34, 2413–2425.
  60. Dufour, C.; Svahn, J. Fanconi anaemia: New strategies. Bone Marrow Transplant. 2008, 41, 90–95.
  61. Inoue, A.; Mori, A.; Yamazaki, S.; Suzuki, R.; Takitani, K.; Tamai, H. Sequential reduced-intensity chemotherapy for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia with rare cytogenetic abnormalities transformed from Fanconi anemia. Pediatr. Int. 2018, 60, 893–894.
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