Revista de Hematología

Contents by Year, Volume and Issue

Table of Contents

General Information

Instructions for Authors

Message to Editor

Editorial Board

>Journals >Revista de Hematología >Year 2013, Issue 4

Jiménez-Mejía AM, Muskus C, Torres JD, Cuéllar-Ambrossi F, Camargo-Guerrero M, Vásquez-Palacio G
Molecular characterization of FLT3-ITD mutations in Colombian patients with acute myelogenous leukemia
Rev Hematol Mex 2013; 14 (4)

Language: Español
References: 22
Page: 166-172
PDF: 454.07 Kb.

Full text


Background: In the past years, several studies detected high frequencies (15-30%) of mutations in the FLT3 gene in AML cases, which has prognosis implications. In Colombia, the frequency and type of mutations in FLT3 in AML cases is still unknown.
Objective: The aim of this study was to determine the frequency and type of mutations in the FLT3 gene that might be involved in the leukomogenesis in a cohort of Colombian AML patients.
Methodology: Descriptive and cohort study made in Colombia genomic DNA was isolated from mononucleated cells of AML patients peripheral blood or bone marrow using QIAamp DNA Blood Mini Kit. Mutations in juxtamembrane and tyrosine kinase domains of FLT3 gene were sequenced.
Results: Thirty-one AML patients were included in the present study. We found 3/31 with FLT3 ITD mutation. The patients with the mutation FLT3 ITD showed higher white blood counts.
Conclusions: This is the first study in Colombia that has been undertaken to determine mutations in FLT3 gene in our population. The frequencies of mutations in FLT3 ITD gene were lower (9.7%) than those informed in the literature. Besides, the presence of FLT3 ITD was associated with higher leukocyte counts in peripheral blood (p=0.023). The results of the present study entail the necessity of multicenter studies in our country to determine the clinical significance of these mutations in the Colombian population.

Key words: Acute myeloid leukemia, FMS Like Tyrosine Kinase (FLT3), PCR.


  1. Vardiman JW, Matutes E, Arber DA, Le Beau MM, Porwit A, Tefferi A, et al. Therapy related myeloid neoplasms. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J,Vardiman JW (eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon: IARC, 2008;127-129.

  2. Patel JP, Gonen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med 2012;366:1079-1089.

  3. Grimwade D, Hills RK, Moorman AV, Walker H, Chatters C, Goldstone AH, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom. Research Council trials. Blood 2010;116:354-365.

  4. Takahashi S. Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia: biology and therapeutic implications. J Hematol Oncol 2011;4:13.

  5. Nakao M, Yokota S, Iwai T, Kaneko H, Horiike S, Kashima K, et al. Internal tandem duplication of the FLT3 gene found in acute myeloid leukemia. Leukemia 1996;10:1911-1918.

  6. Hatzimichael E, Georgiou G, Benetatos L, Briasoulis E. (Review Article) Gene mutations and molecularly targeted therapies in acute myeloid leukemia. Am J Blood Res 2013;3:29-51.

  7. Renneville A, Roumier C, Biggio V, Nibourel O, Boissel N, Fenaux P, et al. Cooperating gene mutation in acute myeloid leukemia: a review of literature. Leukemia 2008;22:915-931.

  8. Schnittger S, Schoch C, Dugas M, Kern W, Staib P, Wuchter C, et al. Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease. Blood 2002;100:59-66.

  9. GLOBOCAN 2008 (IARC) Section of cancer information (26762013)

  10. Instituto Nacional de Cancerología. Anuario estadístico 2008, Santafé de Bogotá, Colombia.

  11. Kiyoi H, Naoe T. FLT3 Mutations in Acute Myeloid Leukemia. Methods in Molecular Medicine, Myeloid Leukemia. Methods and Protocols 2006;125:189-197.

  12. Ruiz-Argüelles GJ, Garcés-Eisele J, Alarcón-Urdaneta C, Lutz-Presno J, Ruiz-Delgado GJ. Primary FMS-like tyrosine kinase 3 (FLT3) mutations in Mexican mestizo patients with de novo acute myelogenous leukemia. Presentado como cartel en XXXIV World Congress-ISH / LIII Congreso Nacional - AMEH, Cancún, abril de 2012. Citado en: Cuervo-Sierra J, Jaime-Pérez JC, Gómez-Almaguer D. Mutaciones del módulo FLT3 en leucemia aguda mieloblástica. Rev Hematol Mex 2012;13:177-184.

  13. Gaich Pamela B, Sastre Darío A, Rodríguez CM. Prevalencia de mutaciones flt3 en leucemias mieloblásticas agudas. www. cobico.com.ar/…dad-científica/publicaciones.

  14. Lucena-Araujo AR, Souza DL, Morato de Oliveira F, Benicio MT, Figueiredo-Pontes LL, Santana-Lemos BA, et al. Results of FLT3 mutation screening and correlations with immunophenotyping in 169 Brazilian patients with acute myeloid leukemia. Annals of Hematology 2010;89:225-228.

  15. Gorin NC, Labopin M, Meloni G, Pigneux A, Esteve J, Mohty M. Impact of FLT3 ITD/NPM1 mutation status in adult patients with acute myelocytic leukemia autografted in first remission. Haematologica 2013;98:e12.

  16. Nazha A, Cortés J, Faderl S, Pierce S, Daver N, Kadia T, et al. Activating internal tandem duplication mutations of the fms-like tyrosine kinase-3 (FLT3-ITD) at complete response and relapse in patients with acute myeloid leukemia. Haematologica 2012;97(8):1242-1245.

  17. Ghanem H, Tank N, Tabbara IA. Prognostic implications of genetic aberrations in acute myelogenous leukemia with normal cytogenetics. Am J Hematol 2012;87:69-77.

  18. Thiede C, Steudel C, Mohr B, Schaich M, Schäkel M, Platzbecker U, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood 2002;99:4326-4335.

  19. Goldschmidt N, Cohen SB, Gatt ME, Safrai M, Rund D. Influence of ethnicity and improved outcome of acute myeloid leukaemia: two decades of follow-up of Israeli patient cohort. Hematol Oncol 2013 Sep. Published online.

  20. Daver N, Strati P, Jabbour E, Kadia T, Luthra R, Wang S, et al. FLT3 mutations in myelodysplastic syndrome and chronic myelomonocytic leukemia. American Journal of Hematology 2013;88:56-59.

  21. Mills KI, Gilkes AF, Walsh V, Sweeney M, Gale R. Rapid and sensitive detection of internal tandem duplication and activating loop mutations of FLT3. British Journal of Haematology 2005;130:203-208.

  22. Gianfelici V, Diverio D, Breccia M, Buffolino S, Derme V, Di Lascio A, et al. A novel point mutation within the juxtamembrane domain of the flt3 gene in acute myeloid leukemia. Ann Hematol 2011;90:845-846.

>Journals >Revista de Hematología >Year 2013, Issue 4

· Journal Index 
· Links 

Copyright 2019