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2022, Number 1

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Rev Cubana Hematol Inmunol Hemoter 2022; 38 (1)

FLT3-ITD biomarker: perspectives and challenges

Garrote SH

Language: Spanish
References: 46
Page: 1-11
PDF size: 245.27 Kb.


ABSTRACT

Introduction: Mutations in the tyrosine kinase 3 gene (FLT3) are of special importance in acute myeloid leukemia because they serve as a guide to confirm the diagnosis, estimate the prognosis, and make therapeutic decisions in the patient. Internal tandem duplication (FLT3-ITD) is the most important alteration of this gene.
Objective: To present the most relevant aspects regarding the FLT3-ITD biomarker in the context of acute myeloid leukemia.
Methods: a search was carried out for updated scientific articles, in English and Spanish, in PubMed, EMBASE, Google Scholar and SciELO. Articles published in the last five years were selected. The most relevant aspects of the biomarker in the context of acute myeloid leukemia, its biological basis, the impact of the size of the fragments and the allelic load in the estimation of the prognosis of the patients, the new therapeutic strategies and the challenges in regarding the laboratory methods for its diagnosis.
Information analysis and synthesis: Beyond the biomarker positivity or not, the size of the ITD, as well as the allelic ratio determined by the mutated allele / wild-type allele, could have a great impact on the prognosis of patients. However, differences persist in the criteria for establishing risk prediction algorithms, the cut-off point to be used as a reference, and the specific laboratory protocol for a more detailed study of the biomarker.
Conclusions: The scientific community needs to continue working to clarify the practical utility of these parameters, validating them in broad and epidemiologically diverse series. The exact cut-off point should be determined as a reference to compare the relationship and standardize the most suitable and feasible laboratory methods for its study.


REFERENCES

  1. Nápoles Méndez D. New interpretations in the classification and diagnosis of pre-eclampsia. MEDISAN. 2016 Abr; 20(4):516-29. Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext& pid=S1029-30192016000400013&lng=es.

  2. Álvarez-Ponce V, Rodríguez-Baquero M, Pardo-Mederos J, Rodríguez-Llobera A. El ácido úrico como factor predictor de la preeclampsia. Rev Cubana Obstet Ginecol. 2018;44(2):[aprox.0p.]. Disponible en: http://revginecobstetricia.sld.cu/index.php/gin/article/view/346.

  3. Anuario estadístico de Cuba 2020. ONEI.2021 jul 14[acceso 05/11/2021];0(0):5-28. Disponible en: Disponible en: http://www.onei.gob.cu/node/16275

  4. Escudero C, Bertoglia P, Muñoz F, Roberts James M. Purinas y ácido úrico en pre-eclampsia: interacciones fisiopatológicas y proyecciones en investigación. Rev. méd. Chile. 2013 Jul;141(7):895-902. DOI: http://dx.doi.org/10.4067/S0034-98872013000700009.

  5. Phipps E, Prasanna D, Jim B. Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines. Clin J Am Soc Nephrol. 2016 Jun;11(6):1102-13. DOI: https://10.2215/CJN.12081115

  6. Yescas Osorio IN, Razo Solano R, Ávila Esquivel JF, Cejudo Álvarez J, Elizalde Valdés VM. Correlación de la concentración sérica de ácido úrico en pacientes con preeclampsia severa en la unidad de cuidados intensivos. Ginecol Obstet Méx. [revista en Internet].2017 [acceso 05/11/2021];85(6):347-54. Disponible en: Disponible en: http://www.scielo.org.mx/scielo.php?script=sci_arttext&pid=S0300-90412017000600347&lng=es .

  7. Lin J, Hong XY, Tu RZ. The value of serum uric acid in predicting adverse pregnancy outcomes of women with hypertensive disorders of pregnancy. Ginekologia Polska. 2018;89(7):375-80. DOI: https://10.5603/GP.a2018.0064

  8. Khaliq O, Konoshita T, Moodley J, Naicker T. The role of uric acid in preeclampsia: Is uric acid a causative factor or sing of preeclampsia? Curr Hypertens Rep. 2018 Jul;20(9):70-80. DOI: https://doi.org/10.1007/s11906-018-0878-7

  9. Brien M E, Duval C, Palacios J, Boufaied I. Uric acid crystals induces placental inflammation and alters trophoblast function via an IL-1-dependent pathway: implication for FGR. J Immunol. 2017 Jul;198(1):443-51. DOI: https://doi:10.4049/jimmunol.1601179.

  10. Fernández A, Castelli J, Hernández N, Soldatti L, Hernández J C. Embarazada con preeclampsia: ácido úrico como biomarcador precoz de gravedad. Salud Militar. 2017 Jul;36(2):6-13. DOI: https://dx.doi.org/10.35954/SM2017.36.2.1

  11. Le TM, Nguyen LH, Phan NL, Le DD, Nguyen H. Maternal serum uric acid concentration and pregnancy outcomes in women with pre- eclampsia/eclampsia. Int J Gynecol Obstet. 2019;144: 21-6. DOI: https://doi.org/10.1002/ijgo.12697

  12. Paci Horno HN, Salman Demarchi MA, Pacheco AB, Zamory ES. Ácido úrico como marcador de complicaciones hipertensivas del embarazo. Bioquinforma Digital. 2020;1:17.Disponible en: https://cobico.com.ar/wp-content/archivos/2020/08/14-%c3%81cido-%c3%9arico-como-marcador-de-complicaciones-hipertensivas-del-embarazo.pdf

  13. Martin A, Faes C, Debevec T, Rytz C, Millet G, Pialoux V. Preterm birth and oxidative stress: Effects of acute physical exercise and hypoxia physiological responses. Redox Biol. 2018 Jul; 17:315-22. DOI: https://10.1016/j.redox.2018.04.022

  14. Dávila-Aliaga C. Neonato de madre con preeclampsia: riesgo para toda la vida. Rev Peru Investig Matern Perinat. 2016;5(1):65-9. DOI: https://doi.org/10.33421/inmp.201657

  15. Machín-García S, Svarch E. Drepanocitosis: 50 años de experiencia en Cuba. Rev Cubana Hematol Inmunol Hemoter. 2017 [acceso 02/03/2021];33(S1):[aprox. 0 p.]. Disponible en: Disponible en: http://www.revhematologia.sld.cu/index.php/hih/article/view/633

  16. Díaz-Morejón L, Rodríguez-Jorge B, García-Sánchez D, León-Rayas Y, Aguilar-Lezcano L, Santacruz-Leonard M. Anemia drepanocítica: características generales de los pacientes a su diagnóstico. Rev Finlay. 2019 [acceso 13/04/2019];9(1):[aprox. 6 p.]. Disponible en: Disponible en: http://www.revfinlay.sld.cu/index.php/finlay/article/view/681

  17. Svarch E. Fisiopatología de la drepanocitosis. Rev Cubana Hematol Inmunol Hemoter. 2009 Abr [acceso 25/02/2021]; 25(1). Disponible en: Disponible en: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0864-02892009000100003&lng=es .

  18. Elenga N, Adeline A, Balcaen J, Vaz T, Calvez M. Pregnancy in Sickle Cell Disease Is a Very High-Risk Situation: An Observational Study. Obstet Gynecol Int. 2016;2016:9069054. DOI: https://10.1155/2016/9069054

  19. Agramonte Llanes OM, Hernández Pdrón C. Atención hematológica a la embarazada con drepanocitosis en el Instituto de Hematología e Inmunología. Rev Cubana Hematol Inmunol Hemoter. 2016 [acceso 18/02/2021];32(1):[aprox. 0 p.]. Disponible en: Disponible en: http://www.revhematologia.sld.cu/index.php/hih/article/view/306

  20. Agramonte Llanes OM, Hernández Padrón C, Roque García W, Núñez García A. Embarazo en la paciente con drepanocitosis: atención integral en el Instituto de Hematología e Inmunología. Rev Cubana Hematol Inmunol Hemoter. 2016 [acceso 18/02/2021];32(2):[aprox. 0 p.]. Disponible en: Disponible en: http://www.revhematologia.sld.cu/index.php/hih/article/view/408

  21. Cardosa D, Ridout A, Nanda S, Howard J, Robinson SE, Oteng-Ntim E. Maternal sickle cell disease and twin pregnancy: a case series and review of the literature. Hematology. 2019 Dec; 24(1):148-58 DOI1. Cabrerizo R, Sánchez D, Gargallo P, Romano V, Montero V. Determinación de la mutación FLT3-ITD por dos métodos en pacientes con leucemia mieloide aguda: comparación e implementación de un nuevo método. Rev Hematología 2019 [acceso 07/03/2021];22(2):134-43. Disponible en: Disponible en: https://revistahematologia.com.ar/index.php/Revista/article/view/17 [ Links ]

  22. Daver N, Schlenk RF, Russell NH, Levis MJ. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 2019;33(2):299-312. DOI: https://10.1038/s41375-018-0357-9 [ Links ]

  23. Adolfsson J, Mansson R, Buza-Vidas N, Hultquist A, Liuba K, Jensen CT, et al. Identification of FLT3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell. 2005;121:295-306. [ Links ]

  24. Larráyoz MJ, Mañú A, Ariceta B, Vázquez I, Aguilera-Díaz A, Fernández-Mercado M, et al. Diagnóstico molecular de alteraciones en el gen FLT3: impacto clínico, retos y propuestas. Genética Médica y Genómica. 2019 [acceso 07/03/2021];3(3):31-9. Disponible en: Disponible en: https://genotipia.com/revista_gm/gmgo013-larrayoz-flt3/ [ Links ]

  25. Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and Management of AML in Adults: 2017 ELN Recommendations from an International Expert Panel. Blood. 2017;129(4):1-55. DOI: https://10.1182/blood-2016-08-733196 [ Links ]

  26. Picharski GL, Andrade DP, Fabro ALMR, Lenzi L, Tonin FS, Ribeiro RC, et al. The Impact of Flt3 Gene Mutations in Acute Promyelocytic Leukemia: A Meta-Analysis. Cancers (Basel). 2019;11(9):1311. DOI: https://10.3390/cancers11091311 [ Links ]

  27. Zhang Y, Zhang Y, Wang F, Wang M, Liu H, Chen X, et al. The mutational spectrum of FLT3 gene in acute lymphoblastic leukemia is different from acute myeloid leukemia. Cancer Gene Ther. 2020;27(1):81-8 DOI: https://10.1038/s41417-019-0120-z [ Links ]

  28. Cheng J, Qu L, Wang J, Cheng L, Wang Y. High expression of FLT3 is a risk factor in leukemia. Mol Med Rep. 2018;(2):2885-92. DOI: https://10.3892/mmr.2017.8232 [ Links ]

  29. Fan Y, Cao Y, Bai X, Zhuang W. The clinical significance of FLT3 ITD mutation on the prognosis of adult acute promyelocytic leukemia. Hematology. 2018;23(7):379-84. DOI: https://10.1080/10245332.2017.1415717 [ Links ]

  30. de Arruda VYN, Matsuzaki LN, Chauffaille ML. FMS-related tyrosine kinase 3 internal tandem duplication (FLT3-ITD): a villain among others. Rev Bras Hematol Hemoter. 2017;39(3):283-4. DOI: https://10.1016/j.bjhh.2017.03.001 [ Links ]

  31. Cao T, Jiang N, Liao H, Shuai X, Su J, Zheng Q. The FLT3-ITD mutation and the expression of its downstream signaling intermediates STAT5 and Pim-1 are positively correlated with CXCR4 expression in patients with acute myeloid leukemia. Sci Rep. 2019;9:12209. https://doi.org/10.1038/s41598-019-48687-z [ Links ]

  32. Nakao M, Iwai T, Kaneko H, Horiike S, Kashima K, Sonoda Y, et al. Internal tandem duplication of the flt3 gene found in acute myeloid leukemia. Leukemia. 1996;10(12):1911-8. [ Links ]

  33. Cornelissen JJ, Blaise D. Hematopoietic stem cell transplantation for patients with AML in first complete remission. Blood. 2016 Jan;127(1):62-70. DOI: https://10.1182/blood-2015-07-604546 [ Links ]

  34. González E, Grille S, Vales V, Boada M, Zanella LM, Leal D, et al. Estudio del ratio de FLT3-ITD como factor pronóstico en leucemias agudas mieloides. Rev Méd Urug. 2016 [acceso 07/03/2021];32(3):145-51. Disponible en: Disponible en: http://www.scielo.edu.uy/scielo.php?script=sci_arttext&pid=S1688-03902016000300003&lng=es [ Links ]

  35. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-405. DOI: https://10.1182/blood-2016-03-643544 [ Links ]

  36. O’Donnell MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Arber DA, et al. Acute Myeloid Leukemia, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15(7):926-57. DOI: https://10.6004/jnccn.2017.0116 [ Links ]

  37. Schranz K, Hubmann M, Harin E, Vosberg S, Herold T, Metzeler KH, et al. Clonal heterogeneity of FLT3-ITD detected by high-throughput amplicon sequencing correlates with adverse prognosis in acute myeloid leukemia. Oncotarget. 2018;9(53):30128-45. DOI: https://10.18632/oncotarget.25729 [ Links ]

  38. Niparuck P, Limsuwanachot N, Pukiat S, Chantrathammachart P, Rerkamnuaychoke B, Magmuang S, et al. Cytogenetics and FLT3-ITD mutation predict clinical outcomes in nontransplant patients with acute myeloid leukemia. Exp Hematol Oncol. 2019;8(3):1-14. DOI: https://10.1186/s40164-019-0127-z [ Links ]

  39. Sakaguchi M, Nakajima N, Yamaguchi H, Najima Y, Shono K, Marumo A, et al. The sensitivity of the FLT3-ITD detection method is an important consideration when diagnosing acute myeloid leukemia. Leuk Res Rep. 2020;13:1-4. DOI: https://10.1016/j.lrr.2020.100198 [ Links ]

  40. Wang A, Hu C, Chen C, Liang X, Wang B, Zou F, et al. Selectively targeting FLT3-ITD mutants over FLT3-wt by a novel inhibitor for acute myeloid leukemia. Hematological. 2021;106(2):605-9. DOI: https://10.3324/haematol.2019.244186 [ Links ]

  41. Sproul AM. Real-time PCR applications in hematology. In: Real-time PCR. Newcastle: Taylor& Francis; 2006. p. 277-301. [ Links ]

  42. Levis MJ, Perl AE, Altman JK, Gocke CD, Bahceci E, Hill J, et al. A next generation sequencing-based assay for minimal residual disease assessment in AML patients with FL T3-ITD mutation. Blood Adv. 2018;2(8):825-31. DOI: https://10.1182/bloodadvances.2018015925 [ Links ]

  43. Patnaik MM. The importance of FL T3 mutational analysis in acute myeloid leukemia. Leuk Lymphoma. 2018;59(10):2273-86. DOI: https://10.1080/10428194.2017.1399312 [ Links ]

  44. Schranz K, Hubmann M, Harin E, Vosberg S, Herold T, Metzeler KH, et al. Clonal heterogeneity of FL T3-ITD detected by high-throughput amplicon sequencing correlates with adverse prognosis in acute myeloid leukemia. Oncotarget. 2018;9(53):30128-45. DOI: https://10.18632/oncotarget.25729 [ Links ]

  45. Sophia Genetics. Myeloid Solution. The state of the art molecular diagnostic application for hematological disorders. 2018 [acceso 07/03/2021]. Disponible en: Disponible en: https://www.sophiagenetics.com [ Links ]

  46. Murphy KM, Levis M, Hafez MJ, Geiger T, Cooper LC, Smith BD, et al. Detection of FLT3 internal tandem duplication and D835 mutations by a multiplex polymerase chain reaction and capillary electrophoresis assay. J Mol Diagn. 2003;5(2):96-102. DOI: https://10.1016/S1525-1578(10)60458-8 [ Links ]: https://10.1080/10245332.2018.1535534




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