J Korean Med Sci.  2010 Jun;25(6):841-845. 10.3346/jkms.2010.25.6.841.

High Transcript Level of FLT3 Associated with High Risk of Relapse in Pediatric Acute Myeloid Leukemia

Affiliations
  • 1Division of Hematology/Oncology, Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. hsahn@snu.ac.kr

Abstract

Identification of prognostic factors and risk-based post-remission therapy was proposed to improve the outcomes of acute myeloid leukemia (AML) and a mutation of FLT3 has been reported to be a risk factor, especially for pediatric patients. Recently, FLT3 expression level was implicated to have prognostic significance in adults, but little is known for childhood AML. To define the prognostic significance, transcript level of FLT3 was analyzed in 52 pediatric AML patients. The median copy number of FLT3 was 4.6x10(3) (40-5.9x10(7) copies)/1.0x10(6) GAPDH copy, and the relapse free survival of patients with high transcript level of FLT3 (>10(6) copy number) (0%) was significantly lower than that of the others (53.2%). High transcript level of FLT3 was associated with a markedly high risk of relapse. The development of new therapeutic scheme such as a frontline allogeneic stem cell transplantation or administration of FLT3 inhibitor is needed to improve outcomes.

Keyword

FLT3; Transcript Level; Leukemia, Myeloid, Acute; Pediatric Age

Figure

  • Fig. 1 The relapse free survival (RFS) of patients with high transcript level of FLT3 (0%) was lower than the RFS of the other patients (53.2±8.0%) (P<0.001).


Cited by  1 articles

Treatment outcome of all-trans retinoic acid/anthracycline combination chemotherapy and the prognostic impact of FLT3/ITD mutation in acute promyelocytic leukemia patients
Seung-Dok Hong, Yeo-Kyeoung Kim, Hee-Nam Kim, Se Ryeon Lee, Jae-Sook Ahn, Deok-Hwan Yang, Je-Jung Lee, Il-Kwon Lee, Myung-Geun Shin, Hyeoung-Joon Kim
Korean J Hematol. 2011;46(1):24-30.    doi: 10.5045/kjh.2011.46.1.24.


Reference

1. Rowe JM, Tallman MS. Intensifying induction therapy in acute myeloid leukemia: has a new standard of care emerged? Blood. 1997. 90:2121–2126.
Article
2. Amadori S, Testi AM, Aricò M, Comelli A, Giuliano M, Madon E, Masera G, Rondelli R, Zanesco L, Mandelli F. The Associazione Italiana Ematologia ed Oncologia Pediatrica Cooperative Group. Prospective comparative study of bone marrow transplantation and postremission chemotherapy for childhood acute myelogenous leukemia. J Clin Oncol. 1993. 11:1046–1054.
3. Ravindranath Y, Yeager AM, Chang MN, Steuber CP, Krischer J, Graham-Pole J, Carroll A, Inoue S, Camitta B, Weinstein HJ. Pediatric Oncology Group. Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. N Engl J Med. 1996. 334:1428–1434.
Article
4. Woods WG, Neudorf S, Gold S, Sanders J, Buckley JD, Barnard DR, Dusenbery K, DeSwarte J, Arthur DC, Lange BJ, Kobrinsky NL. Children's Cancer Group. A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission. Blood. 2001. 97:56–62.
5. Meshinchi S, Arceci RJ. Prognostic factors and risk-based therapy in pediatric acute myeloid leukemia. Oncologist. 2007. 12:341–355.
Article
6. Meshinchi S, Smith FO, Arceci RJ. Prognostic factors and risk-based therapy in pediatric acute myeloid leukemia. Curr Oncol Rep. 2003. 5:489–497.
Article
7. Löwenberg B, Griffin JD, Tallman MS. Acute myeloid leukemia and acute promyelocytic leukemia. Hematology Am Soc Hematol Educ Program. 2003. 82–101.
8. Iwai T, Yokota S, Nakao M, Okamoto T, Taniwaki M, Onodera N, Watanabe A, Kikuta A, Tanaka A, Asami K, Sekine I, Mugishima H, Nishimura Y, Koizumi S, Horikoshi Y, Mimaya J, Ohta S, Nishikawa K, Iwai A, Shimokawa T, Nakayama M, Kawakami K, Gushiken T, Hyakuna N, Fujimoto T. Children's Cancer and Leukemia Study Group, Japan. Internal tandem duplication of the FLT3 gene and clinical evaluation in childhood acute myeloid leukemia. Leukemia. 1999. 13:38–43.
Article
9. Kang HJ, Hong SH, Kim IH, Park BK, Han KS, Cho HI, Shin HY, Ahn HS. Prognostic significance of FLT3 mutations in pediatric non-promyelocytic acute myeloid leukemia. Leuk Res. 2005. 29:617–623.
Article
10. Kondo M, Horibe K, Takahashi Y, Matsumoto K, Fukuda M, Inaba J, Kato K, Kojima S, Matsuyama T. Prognostic value of internal tandem duplication of the FLT3 gene in childhood acute myelogenous leukemia. Med Pediatr Oncol. 1999. 33:525–529.
Article
11. Liang DC, Shih LY, Hung IJ, Yang CP, Chen SH, Jaing TH, Liu HC, Chang WH. Clinical relevance of internal tandem duplication of the FLT3 gene in childhood acute myeloid leukemia. Cancer. 2002. 94:3292–3298.
12. Meshinchi S, Woods WG, Stirewalt DL, Sweetser DA, Buckley JD, Tjoa TK, Bernstein ID, Radich JP. Prevalence and prognostic significance of Flt3 internal tandem duplication in pediatric acute myeloid leukemia. Blood. 2001. 97:89–94.
Article
13. Stirewalt DL, Kopecky KJ, Meshinchi S, Appelbaum FR, Slovak ML, Willman CL, Radich JP. FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood. 2001. 97:3589–3595.
Article
14. Xu F, Taki T, Yang HW, Hanada R, Hongo T, Ohnishi H, Kobayashi M, Bessho F, Yanagisawa M, Hayashi Y. Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children. Br J Haematol. 1999. 105:155–162.
Article
15. Zwaan CM, Meshinchi S, Radich JP, Veerman AJ, Huismans DR, Munske L, Podleschny M, Hählen K, Pieters R, Zimmermann M, Reinhardt D, Harbott J, Creutzig U, Kaspers GJ, Griesinger F. FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellular drug resistance. Blood. 2003. 102:2387–2394.
Article
16. Bornhäuser M, Illmer T, Schaich M, Soucek S, Ehninger G, Thiede C. AML SHG 96 study group. Improved outcome after stem-cell transplantation in FLT3/ITD-positive AML. Blood. 2007. 109:2264–2265.
17. Gale RE, Hills R, Kottaridis PD, Srirangan S, Wheatley K, Burnett AK, Linch DC. 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.
Article
18. Meshinchi S, Arceci RJ, Sanders JE, Smith FO, Woods WB, Radich JP, Alonzo TA. Role of allogeneic stem cell transplantation in FLT3/ITD-positive AML. Blood. 2006. 108:400–401.
Article
19. Kuchenbauer F, Kern W, Schoch C, Kohlmann A, Hiddemann W, Haferlach T, Schnittger S. Detailed analysis of FLT3 expression levels in acute myeloid leukemia. Haematologica. 2005. 90:1617–1625.
20. Ozeki K, Kiyoi H, Hirose Y, Iwai M, Ninomiya M, Kodera Y, Miyawaki S, Kuriyama K, Shimazaki C, Akiyama H, Nishimura M, Motoji T, Shinagawa K, Takeshita A, Ueda R, Ohno R, Emi N, Naoe T. Biologic and clinical significance of the FLT3 transcript level in acute myeloid leukemia. Blood. 2004. 103:1901–1908.
Article
21. Kang HJ, Shin HY, Choi HS, Han KS, Ahn HS. Autologous peripheral blood stem cell transplantation with BCVAC conditioning in childhood acute myeloid leukemia. Bone Marrow Transplant. 2004. 33:471–476.
Article
22. Shenoy S, Smith FO. Hematopoietic stem cell transplantation for childhood malignancies of myeloid origin. Bone Marrow Transplant. 2008. 41:141–148.
Article
23. Ebb DH, Weinstein HJ. Diagnosis and treatment of childhood acute myelogenous leukemia. Pediatr Clin North Am. 1997. 44:847–862.
Article
24. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A. The Medical Research Council Adult and Children's Leukaemia Working Parties. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. Blood. 1998. 92:2322–2333.
Article
25. Birg F, Courcoul M, Rosnet O, Bardin F, Pébusque MJ, Marchetto S, Tabilio A, Mannoni P, Birnbaum D. Expression of the FMS/KIT-like gene FLT3 in human acute leukemias of the myeloid and lymphoid lineages. Blood. 1992. 80:2584–2593.
Article
26. Drexler HG. Expression of FLT3 receptor and response to FLT3 ligand by leukemic cells. Leukemia. 1996. 10:588–599.
27. Doepfner KT, Boller D, Arcaro A. Targeting receptor tyrosine kinase signaling in acute myeloid leukemia. Crit Rev Oncol Hematol. 2007. 63:215–230.
Article
28. Knapper S. FLT3 inhibition in acute myeloid leukaemia. Br J Haematol. 2007. 138:687–699.
Article
Full Text Links
  • JKMS
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr