Entrar/Registro  
INICIO ENGLISH
 
Revista de Hematología
   
MENÚ

Contenido por año, Vol. y Num.

Índice de este artículo

Información General

Instrucciones para Autores

Mensajes al Editor

Directorio






>Revistas >Revista de Hematología >Año 2015, No. 2


Lagunas-Rangel FA, Pérez-Contreras VA, Cortés-Penagos C
FLT3, NPM1 y C/EBPα como marcadores de pronóstico en pacientes con leucemia mieloide aguda
Rev Hematol Mex 2015; 16 (2)

Idioma: Español
Referencias bibliográficas: 44
Paginas: 152-167
Archivo PDF: 801.49 Kb.


Texto completo




RESUMEN

La leucemia mieloide aguda es un grupo de enfermedades fenotípica y genéticamente heterogéneas, originadas por la acumulación de mutaciones en una célula madre hematopoyética o célula progenitora. De manera tradicional, los estudios citogenéticos se han utilizado para estratificar a los pacientes con leucemia mieloide aguda en tres categorías: favorable, intermedio y desfavorable. Sin embargo, la estratificación pronóstica y la decisión del tratamiento para los pacientes que tienen cariotipo normal muestra dificultades debido a la alta heterogeneidad clínica. Recientemente, la identificación de mutaciones genéticas adicionales a los marcadores clásicos permitió generar nuevas entidades en el grupo de leucemia mieloide aguda respecto al tratamiento y seguimiento de esta enfermedad. En 2008, la Organización Mundial de la Salud introdujo las mutaciones en NPM1 y C/EBPα como entidades dentro del grupo de leucemia mieloide aguda con anormalidades genéticas recurrentes, mientras que las mutaciones en el gen FLT3 se han descrito como de mal pronóstico en los pacientes portadores. El conocimiento de estas mutaciones no sólo apoya el seguimiento de esta enfermedad, sino que abre la posibilidad de generar nuevas estrategias de tratamiento.


Palabras clave: leucemia mieloide aguda, marcador molecular, pronóstico, proliferación, diferenciación celular.


REFERENCIAS

  1. Estey E, Döhner H. Acute myeloid leukaemia. Lancet 2006;368:1894-1907. Available at: http://www.sciencedirect.com/science/article/pii/S0140673606697808. Accessed August 29, 2014.

  2. Takahashi S. Current findings for recurring mutations in acute myeloid leukemia. J Hematol Oncol 2011;4:36. doi:10.1186/1756-8722-4-36.

  3. Deguchi K, Gilliland DG. Cooperativity between mutations in tyrosine kinases and in hematopoietic transcription factors in AML. Leukemia 2002;16:740-744. doi:10.1038/sj.leu.2402500.

  4. Becker H, Pfeifer D, Afonso JD, Nimer SD, et al. Two cell lines of t(8;21) acute myeloid leukemia with activating KIT exon 17 mutation: models for the “second hit” hypothesis. Leukemia 2008;22:1792-1794. doi:10.1038/leu.2008.61.

  5. Jordan CT. Unique molecular and cellular features of acute myelogenous leukemia stem cells. Leukemia 2002;16:559-562. doi:10.1038/sj.leu.2402446.

  6. Martelli MP, Sportoletti P, Tiacci E, Martelli MF, Falini B. Mutational landscape of AML with normal cytogenetics: biological and clinical implications. Blood Rev 2013;27:13-22. doi:10.1016/j.blre.2012.11.001.

  7. Swerdlow SH, Campo E, Harris NL, Jaffe ES, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4a ed. Lyon: International Agency for Research on Cancer (IARC), 2008.

  8. Rubnitz JE, Gibson B, Smith FO. Acute myeloid leukemia. Hematol Oncol Clin North Am 2010;24:35-63. doi:10.1016/j.hoc.2009.11.008.

  9. Stirewalt DL, Radich JP. The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer 2003;3:650-665. doi:10.1038/nrc1169.

  10. Small D. FLT3 mutations: biology and treatment. Hematology Am Soc Hematol Educ Program 2006:178-184. doi:10.1182/asheducation-2006.1.178.

  11. Levis M, Small D. FLT3: ITDoes matter in leukemia. Leukemia 2003;17:1738-1752. doi:10.1038/sj.leu.2403099.

  12. Lyman SD, Jacobsen SE. c-kit ligand and Flt3 ligand: stem/progenitor cell factors with overlapping yet distinct activities. Blood 1998;91:1101-1134. Available at: http://bloodjournal.hematologylibrary.org/content/91/4/1101. short. Accessed October 22, 2014.

  13. Rosnet O, Matteï M-G, Marchetto S, Birnbaum D. Isolation and chromosomal localization of a novel FMS-like tyrosine kinase gene. Genomics 1991;9:380-385. doi:10.1016/0888-7543(91)90270-O.

  14. Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood 2002;100:1532-1542. doi:10.1182/blood-2002-02-0492.

  15. Meshinchi S, Appelbaum FR. Structural and functional alterations of FLT3 in acute myeloid leukemia. Clin Cancer Res 2009;15:4263-4269. doi:10.1158/1078-0432.CCR-08-1123.

  16. Griffith J, Black J, Faerman C, Swenson L, et al. The structural basis for autoinhibition of FLT3 by the juxtamembrane domain. Mol Cell 2004;13:169-178. doi:10.1016/S1097-2765(03)00505-7.

  17. Kayser S, Schlenk RF, Londono MC, Breitenbuecher F, et al. Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome. Blood 2009;114:2386-2392. doi:10.1182/blood-2009-03-209999.

  18. Chan PM. Differential signaling of Flt3 activating mutations in acute myeloid leukemia: a working model. Protein Cell 2011;2:108-115. doi:10.1007/s13238-011-1020-7.

  19. Nakao M, Yokota S, Iwai T, Kaneko H, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia 1996;10:1911-1818. Available at: http://www.ncbi.nlm.nih.gov/pubmed/8946930. Accessed October 31, 2014.

  20. Parcells BW, Ikeda AK, Simms-Waldrip T, Moore TB, Sakamoto KM. FMS-like tyrosine kinase 3 in normal hematopoiesis and acute myeloid leukemia. Stem Cells 2006;24:1174-1184. doi:10.1634/stemcells.2005-0519.

  21. Kiyoi H, Towatari M, Yokota S, Hamaguchi M, et al. Internal tandem duplication of the FLT3 gene is a novel modality of elongation mutation which causes constitutive activation of the product. Leukemia 1998;12:1333-1337.

  22. Meshinchi S, Stirewalt DL, Alonzo TA, Boggon TJ, et al. Structural and numerical variation of FLT3/ITD in pediatric AML. Blood 2008;111:4930-4933. doi:10.1182/blood-2008-01-117770.

  23. Levis M. FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013? Hematology Am Soc Hematol Educ Program 2013;2013:220-226. doi:10.1182/asheducation-2013.1.220.

  24. Li L, Bailey E, Greenblatt S, Huso D, Small D. Loss of the wild-type allele contributes to myeloid expansion and disease aggressiveness in FLT3/ITD knockin mice. Blood 2011;118:4935-4945. doi:10.1182/blood-2011-01-328096.

  25. Stirewalt DL, Kopecky KJ, Meshinchi S, Engel JH, et al. Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia. Blood 2006;107:3724-3726.

  26. Ponziani V, Gianfaldoni G, Mannelli F, Leoni F, et al. The size of duplication does not add to the prognostic significance of FLT3 internal tandem duplication in acute myeloid leukemia patients. Leukemia 2006;20:2074-2076. doi:10.1038/sj.leu.2404368.

  27. Gale RE, Green C, Allen C, Mead AJ, et al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood 2008;111:2776-2784. doi:10.1182/blood-2007-08-109090.

  28. Libura M, Asnafi V, Tu A, Delabesse E, et al. FLT3 and MLL intragenic abnormalities in AML reflect a common category of genotoxic stress. Blood 2003;102:2198-2204. doi:10.1182/blood-2003-01-0162.

  29. Grisendi S, Mecucci C, Falini B, Pandolfi PP. Nucleophosmin and cancer. Nat Rev Cancer 2006;6:493-505. doi:10.1038/nrc1885.

  30. Falini B, Nicoletti I, Bolli N, Martelli MP, et al. Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias. Haematologica 2007;92:519-532. Available at: http://www.ncbi.nlm.nih.gov/pubmed/17488663. Accessed November 19, 2014.

  31. Falini B, Nicoletti I, Martelli MF, Mecucci C. Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+AML): biologic and clinical features. Blood 2007;109:874-885. doi:10.1182/blood-2006-07-012252.

  32. Burgess RJ, Zhang Z. Histone chaperones in nucleosome assembly and human disease. Nat Struct Mol Biol 2013;20:14-22. doi:10.1038/nsmb.2461.

  33. Verhaak RG, Goudswaard CS, van Putten W, Bijl MA, et al. Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance. Blood 2005;106:3747-3754. doi:10.1182/blood-2005-05-2168.

  34. Falini B, Bolli N, Liso A, Martelli MP, et al. Altered nucleophosmin transport in acute myeloid leukaemia with mutated NPM1: molecular basis and clinical implications. Leukemia 2009;23:1731-1743. doi:10.1038/leu.2009.124.

  35. Chou WC, Tang JL, Wu SJ, Tsay W, et al. Clinical implications of minimal residual disease monitoring by quantitative polymerase chain reaction in acute myeloid leukemia patients bearing nucleophosmin (NPM1) mutations. Leukemia 2007;21:998-1004. doi:10.1038/sj.leu.2404637.

  36. Gorello P, Cazzaniga G, Alberti F, Dell’Oro MG, et al. Quantitative assessment of minimal residual disease in acute myeloid leukemia carrying nucleophosmin (NPM1) gene mutations. Leukemia 2006;20:1103-1108. doi:10.1038/sj.leu.2404149.

  37. Leroy H, Roumier C, Huyghe P, Biggio V, et al. CEBPA point mutations in hematological malignancies. Leukemia 2005;19:329-334. doi:10.1038/sj.leu.2403614.

  38. Pabst T, Mueller BU, Zhang P, Radomska HS, et al. Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-alpha (C/EBPalpha), in acute myeloid leukemia. Nat Genet 2001;27:263-270. doi:10.1038/85820.

  39. Bienz M, Ludwig M, Leibundgut EO, Mueller BU, et al. Risk assessment in patients with acute myeloid leukemia and a normal karyotype. Clin Cancer Res 2005;11:1416-1424. doi:10.1158/1078-0432.CCR-04-1552.

  40. Nerlov C. C/EBPalpha mutations in acute myeloid leukaemias. Nat Rev Cancer 2004;4:394-400. doi:10.1038/nrc1363.

  41. Pabst T, Mueller BU. Complexity of CEBPA dysregulation in human acute myeloid leukemia. Clin Cancer Res 2009;15:5303-5307. doi:10.1158/1078-0432.CCR-08-2941.

  42. Gregory TK, Wald D, Chen Y, Vermaat JM, et al. Molecular prognostic markers for adult acute myeloid leukemia with normal cytogenetics. J Hematol Oncol 2009;2:23. doi:10.1186/1756-8722-2-23.

  43. Kelly LM, Gilliland DG. Genetics of myeloid leukemias. Annu Rev Genomics Hum Genet 2002;3:179-198. doi:10.1146/annurev.genom.3.032802.115046.

  44. Abu-Duhier FM, Goodeve AC, Wilson GA, Care RS, et al. Genomic structure of human FLT3: implications for mutational analysis. Br J Haematol 2001;113:1076-1077. doi:10.1046/j.1365-2141.2001.02821.x.



>Revistas >Revista de Hematología >Año2015, No. 2
 

· Indice de Publicaciones 
· ligas de Interes 






       
Derechos Resevados 2019