Associations Between Age, Cytogenetics, FLT3-ITD, and Marrow Leukemia Cells Identified by Flow Cytometry

  • Su, Long (Cancer Center, the First Hospital, Jilin University) ;
  • Gao, Su-Jun (Cancer Center, the First Hospital, Jilin University) ;
  • Tan, Ye-Hui (Cancer Center, the First Hospital, Jilin University) ;
  • Han, Wei (Cancer Center, the First Hospital, Jilin University) ;
  • Li, Wei (Cancer Center, the First Hospital, Jilin University)
  • Published : 2013.09.30


Objectives: To explore the relationships between age, cytogenetic subgroups, molecular markers, and cells with leukemic aberrant immunophenotype in patients with acute myeloid leukemia (AML). Methods: In this study, we evaluated the correlations between age, cytogenetic subgroups (normal, balanced and unbalance karyotype), molecular mutations (NPM1, FLT3-ITD, and CEBPA mutations) and marrow leukemia cells (LC) identified by flow cytometry in 256 patients with de novo AML. Results: From age group 10-19 years to age group ${\geq}60$ years, the percentage of LC decreased from $67.0{\pm}18.4%$ to $49.0{\pm}25.1%$ (F=2.353, P=0.041). LC percentage was higher in patients with balanced karyotypes ($65.7{\pm}22.4%$), than those with unbalanced karyotypes ($46.0{\pm}26.6%$) (u=3.444, P=0.001) or a normal karyotype ($49.9{\pm}22.1%$) (u=5.093, P<0.001). Patients with FLT3-ITD ($64.3{\pm}19.5%$) had higher LC percentages compared with those without ($54.2{\pm}24.3%$) (u=2.794, P=0.007). Conclusions: Associations between age, cytogenetics, molecular markers, and marrow leukemia cells may offer beneficial information to understand the biology and pathogenesis of AML.


  1. Appelbaum FR, Gundacker H, Head DR, et al (2006). Age and acute myeloid leukemia. Blood, 107, 3481-5.
  2. Gardini A, Cesaroni M, Luzi L, et al (2008). AML1/ETO oncoprotein is directed to AML1 binding regions and colocalizes with AML1 and HEB on its tar gets. PloS Genet, 4, e1000275.
  3. Gilliland DG, Grifn JD (2002). Role of FLT3 in leukemia. Curr Opin Hematol, 9, 274-81.
  4. Grisolano JL, Wesselschmidt RL, Pelicci PG, et al (1997). Altered myeloid development and acute leukemia in transgenic mice expressing PML-RAR under control of cathepsin G regulatory sequences. Blood, 89, 376-87.
  5. Haferlach T, Bacher U, Alpermann T, et al (2012). Amount of bone marrow blasts is strongly correlated to NPM1 and FLT3-ITD mutation rate in AML with normal karyotype. Leuk Res, 36, 51-8.
  6. Hayakawa F, Towatari M, Kiyoi H, et al (2000). Tandemduplicated Flt3 constitutively activates STAT5 and MAP kinase and introduces autonomous cell growth in IL-3- dependent cell lines. Oncogene, 19, 624-31.
  7. Hollink IH, Zwaan CM, Zimmermann M, et al (2009). Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML. Leukemia, 23, 262-70.
  8. ISCN (2009). An international system for human cytogenetic nomenclature. Shaffer LG, Slovak ML, Campbell LJ, eds. S. Krager; Basel.
  9. Kaleem Z, Crawford E, Pathan MH, et al (2003). Flow cytometric analysis of acute leukemias. Diagnostic utility and critical analysis of data. Arch Pathol Lab Med, 127, 42-8.
  10. Kaleem Z, Crawford E, Pathan MH, et al (2003). Flow cytometric analysis of acute leukemias. Diagnostic utility and critical analysis of data. Arch Pathol Lab Med, 127, 42-8.
  11. Li Y, Gao L, Luo X, et al (2013). Epigenetic silencing of microRNA-193a contributes to leukemogenesis in t(8;21) acute myeloid leukemia by activating the PTEN/PI3K signal pathway. Blood, 121, 499-509.
  12. Mizuki M, Fenski R, Halfter H, et al (2000). Flt3 mutations from patients with acute myeloid leukemia induce transformation of 32D cells mediated by the RAS and STAT5 pathway. Blood, 96, 3907-14.
  13. Park SH, Chi HS, Min SK, et al (2011). Prognostic impact of c-KIT mutations in core binding factor acute myeloid leukemia. Leuk Res, 35, 1376- 83.
  14. Puccetti E, Ruthardt M (2004). Acute promyelocytic leukemia: PML/$RAR\alpha$and the leukemia stem cell. Leukemia, 18, 1169-75.
  15. Rajaraman R, Guernsey DL, Rajaraman MM, et al (2006). Stem cells, senescence, neosis and self-renewal in cancer. Cancer Cell Int, 6, 25.
  16. Schneider F, Hoster E, Schneider S, et al (2012). Age-dependent frequencies of NPM1 mutations and FLT3-ITD in patients with normal karyotype AML (NK-AML). Ann Hematol, 91, 9-18.
  17. Schnittger S, Schoch C, Dugas M, et al (2002). 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, 100, 59-66.
  18. Schnittger S, Schoch C, Kern W, et al (2005). Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype. Blood, 106, 3733-9.
  19. Steffen B, Knop M, Bergholz U, et al (2011). AML1/ETO induces self-renewal in hematopoietic progenitor cells via the Groucho-related amino-terminal AES protein. Blood, 117, 4328-37.
  20. Su L, Gao S, Li W, et al (2013). Age-specific distributions of cytogenetic subgroups of acute myeloid leukemia: data analysis in a Chinese population. Acta Haematol, 129, 175-81.
  21. Thiede C, Steudel C, Mohr B, et al (2002). Analysis of FLT3- activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood, 99, 4326-35.
  22. Wang YY, Zhao LJ, Wu CF, et al (2011). C-KIT mutation cooperates with full-length AML1-ETO to induce acute myeloid leukemia in mice. Proc Natl Acad Sci USA, 108, 2450-5.
  23. Wouters BJ, Löwenberg B, Erpelinck-Verschueren CA, et al (2009). Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood, 113, 3088-91.

Cited by

  1. Cytogenetic and Genetic Mutation Features of de novo Acute Myeloid Leukemia in Elderly Chinese Patients vol.15, pp.2, 2014,
  2. Survival Outcome of AML Patients with and without TKD Mutations vol.15, pp.24, 2015,
  3. Overall Survival in Acute Myeloid Leukaemia Patients with and without Internal Tandem Duplication vol.16, pp.1, 2015,
  4. Characterisation and Clinical Significance of FLT3-ITD and non-ITD in Acute Myeloid Leukaemia Patients in Kelantan, Northeast Peninsular Malaysia vol.16, pp.12, 2015,
  5. Characterization of CEBPA Mutations and Polymorphisms and their Prognostic Relevance in De Novo Acute Myeloid Leukemia Patients vol.16, pp.9, 2015,
  6. Outcome of Inversion 16 in TKD Positive and Negative Acute Myeloid Leukemia Patients vol.17, pp.4, 2016,