2012, Number 4
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Rev Hematol Mex 2012; 13 (4)
FLT3 domain mutations in acute myelogenous leukemia
Cuervo-Sierra J, Jaime-Pérez JC, Gómez-Almaguer D
Language: Spanish
References: 43
Page: 177-184
PDF size: 214.80 Kb.
ABSTRACT
Acute myeloblastic leukemia (AML) has a high morbility and mortality related to high early relapse rates and frequent refractory disease.
Among the prognostic factors used for stratifying the disease risk are the age, the white blood cell count at diagnosis, the cytogenetics, the
AML etiology ( chemotherapy related or neoplasia related); despite these factors there is no accurate marker to define risk of refractory or
uncontrolled disease. The FLT3 receptor mutations, specifically internal tandem duplication mutations (ITD-FLT3), have been associated
with adverse outcome and high relapse rates despite the intensive treatment schemes including chemotherapy plus specific FLT3 inhibitors
or allogeneic stem cell transplantation. Attemps to correlate FLT3 mutations with cytogenetics have found several associations between
normal cytogenetics or intermediate risk and the ITD-FLT3 mutations, some favor the prognostic and others do not. Currently there are investigations
trying to define the role of the FLT3 inhibitors and other drugs directed to overcome the different pathophysiological mechanisms
involved in AML. This article is intended to review the state of knowledge of FLT3 mutations and its impact on the clinical course of AML.
REFERENCES
Ahmedin J, Rebecca S, Jiaquan Xu. Cancer Statistics 2010. CA Cancer J Clin 2010; 60;277-300;
Crespo E. Epidemiología de las leucemias agudas. Rev Hematol Mex 2010;11: S37-S39.
Rowe JM. Optimal induction and post-remission therapy for AML in first remission. Hematology 2009;396-405.
Deschler B, Lübbert M. Acute Myeloid Leukemia: epidemiology and oncology. Cancer 2006;107(9):2099-20107.
Harry PE. Prognostic Factors in Elderly Patients with AML and the Implications for Treatment. Hematology 2007;420-428.
Small D. FLT3 mutations: Biology and treatment. American Society of Hematology Educational Book, 2006;178-184.
Meshinchi S, Woods WG, et al. Prevalence and prognostic significance of FLT3 internal tandem duplication in pediatric acute myeloid leukemia. Blood 2001;97:89-94.
Kim YK, Lee JJ, Lee YR, et al. The presence of FLT3/ITD mutations is an independent prognostic factor in acute myeloid leukemia patients with normal karyotype. Blood 2004;104:3008a.
Shih LY, Huang CF, Wu JH et al. Internal tandem duplication of FLT3 in relapsed acute myeloid leukemia: a comparative analysis of bone marrow samples of 108 adult patients at diagnosis and relapse. Blood. 2002; 100:2387-2392
Ravandi F, Kantarjian H, Faderl S, et al. Outcome of patients with FLT3-mutated acute myeloid leukemia in first relapse. Leuk Res 2010;34(6):752-726.
Mead A, Linch D, Hills R, et al. Favourable prognosis associated with FLT3 tyrosine kinase domain mutations in AML in contrast to the adverse outcome associated with internal tandem duplications. Blood 2005;106:334a.
Small D. Targeting FLT3 for treatment of leukemia. Semin Hematol 2008;45 (Suppl 2): S17-S21.
Yanada M, Matsuo K, Suzuki T, et al. Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis. Leukemia 2005;19:1345-1349.
Ruiz-Argüelles GJ. Promyelocytic Leukemia in Mexican Mestizos. Blood 1997;89 (1):348-348.
Buitrón-Santiago N, Arteaga-Ortiz L, Rosas-López A, Aguayo A, López-Karpovitch X, Crespo-Solís E. Acute myeloid leukemia in adults: experience at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán from 2003 to 2008. Rev Invest Clin 2010;62(2):100-108.
Gómez-Guijosa M, Gutiérrez-Aguirre CH, Cantú-Rodríguez OG, et al. Leucemia promielocítica aguda. Resultados del tratamiento en el Hospital Universitario de la UANL, Monterrey, México. Medicina Universitaria 2009;11(44):165-169
Krum E, Yamamoto M, Lopes Ferrar M, et al. Prevalence of FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD+) in de novo acute myeloid leukemia patients categorized according to cytogenetic risk. Sao Paulo Med J 2009;127(1):23-27.
Lucena-Araujo AR, Souza DL, Morato de Oliveira F, et al. Results of FLT3 mutation screening and correlations with immunophenotyping in 169 Brazilian patients with acute myeloid leukemia. Ann Hematol 2010;89(2):225-228.
Arana-Trejo RM. FLT3 gene internal tandem duplication (ITD) mutations in patients with acute myeloid leukemia (AML). Presented as abstract at Highlights from ISH 2007.
Ruiz-Arguelles 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.
Jiménez AM ,Torres JD, Cuéllar F, Muskus C, Camargo M, Vásquez-Palacio G. Determinación de las mutaciones en los genes FLT3 y NPM1 en pacientes con leucemia mieloide aguda. Iatreia 2010;23;4-S.
Gaich P, Sastre D, Rodríguez C. Prevalencia de mutaciones FLT3 en leucemias mieloblásticas agudas. Laboratorio de Oncohematología, Hospital Nacional de Clínicas-Facultad de Ciencias Médicas- Universidad Nacional de Córdoba (Argentina). Publicado en Primer Congreso Bioquímico de Córdoba 2011.
Santamaría-Quesada C, Vargas M, Venegas P, et al. Molecular and Epidemiologic Findings of Childhood Acute Leukemia in Costa Rica. J Pediatr Hematol Oncol 2009;31(2).
Kiyoi H, Towatari M, Yokota S, 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.
Ravandi F, Kantarjian H, Faderl S, et al. Outcome of patients with FLT3-mutated acute myeloid leukemia in first relapse. Leuk Res 2010;34(6):752-756. Epub 2009 Oct 29.
Schnittger S, Bacher U, Haferlach C, et al. Clinical impact of FLT3 mutation load in acute promyelocytic leukemia with t(15;17)/PML-RARA. Haematologica 2011; 96(12):1799-1807.
Patel J, Gonen M, Figueroa ME, et al. Prognostic Relevance of Integrated Genetic Profiling in Acute Myeloid Leukemia. N Engl J Med 2012;366:1079-1089.
Stone RM, Fischer T, Paquette R, et al. A Phase 1b study of midostaurin (PKC412) in combination with daunorubicin and cytarabine induction and high-dose cytarabine consolidation in patients under age 61 with newly diagnosed de novo acute myeloid leukemia: overall survival of patients whose blasts have FLT3 mutations is similar to those with wild-type FLT3. Blood 2009;114:263.
Stone RM, Dohner H, Ehninger G, Villeneuve M, Teasdale T, Virkus JD, et al. CALGB 10603 (RATIFY): a randomized phase III study of induction (daunorubicin/cytarabine) and consolidation (high-dose cytarabine) chemotherapy combined with midostaurin or placebo in treatment-naive patients with FLT3 mutated AML. J Clin Oncol 2011;29:31s.
Levis M, Ravandi F, Wang ES, Baer MR, Perl A, Coutre S, et al. Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. Blood 2011;117: 294-3301.
Knapper S, Burnett AK, Hills RK, Small D, Levis M. Lestaurtinib FLT3 inhibitory activity is modulated by concomitant azole therapy and may influence relapse risk. Blood 2009;114:326.
Ravandi F, Cortes JE, Jones D, Faderl S, Garcia-Manero G, Konopleva MY, et al. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol 2010;28:1856-1862.
Trikha M, Cortes J, Foran J, Ghirdaladze D, DeVetten M, Zodelava M, et al. AC220, a potent, selective, second-generation FLT3 receptor tyrosine kinase inhibitor in a first-in-human phase 1 AML study. Haematologica 2010;96:460-461.
Kelly LM, Yu JC, Boulton CL, Apatira M, Li J, Sullivan CM, et al. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell 2002;1:421-432.
Zeng Z, Shi YX, Samudio IJ, Wang RY, Ling X, Frolova O, et al. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML. Blood 2009;113:6215-6224.
Youssoufian H, Rowinsky EK, Tonra J, Li Y, Targeting FMS. Related tyrosine kinase receptor 3 with the human immunoglobulin G1 monoclonal antibody IMC-EB10. Cancer 2010;116:1013-1017.
Meshinchi S, Arceci RJ, Sanders JE, et al. Role of allogeneic stem cell transplantation in FLT3/ITD-positive AML. Blood 2006;108:400.
Bornhauser M, Illmer T, Schaich M, et al. Improved outcome after stem-cell transplantation in FLT3/ITD-positive AML. Blood 2007;109:2265-2266.
Brunet S, Perea G, Esteve J, et al. Adverse impact of FLT3 internal tandem duplication in patients with poor-risk acute myeloid leukaemia allocated to autologous transplantation. Bone Marrow Transpl 2004;33:S3 (Suppl 1; abstr 71).
Gale R, Hills R, Kottaridis P, et al. No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): An analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML10 and 12 trials. Blood 2005;106:3658-3665.
Brunet S, Labopin M, Esteve J, et al. Impact of FLT3 Internal Tandem Duplication on the Outcome of Related and Unrelated Hematopoietic Transplantation for Adult Acute Myeloid Leukemia in First Remission: A Retrospective Analysis. J Clin Oncol 2012;30:735-741.
Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 2009;361:1249-1259.
Zhu, et al. Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights. J Hematol Oncol 2010;3:17.