Meta analysis on the relationship between cuplike nuclei morphology and FLT3-ITD mutation in acute myeloid leukemia

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Author:
ZHUANG Qian(Department of Hemologic Laboratory, Shengjing Hospital of China Medical University, Shenyang 110022, China)
HAO Liang-chun(Department of Hemologic Laboratory, Shengjing Hospital of China Medical University, Shenyang 110022, China)
CHEN Fang()
ZHANG Ji-hong()
Journal Title:
Journal of Leukemia & Lymphoma
Issue:
Volume 21, Issue 02, 2012
DOI:
10.3760/cma.j.issn.1009-9921.2012.02.010
Key Word:
Meta analysis;Cuplike nuclei cell;Leukemia,myeloid,acute;FLT3-ITD mutation

Abstract: Objective To investigate the association between cuplike nuclei morphology and FLT3-ITD mutation, so as to provide evidence for the minor classification of AML. Methods The articles on the association of cuplike nuclei morphology and FLT3-ITD mutation were retrieved by searching international and national databases from 1999 to 2011. The relationship was assessed by meta analysis with Statal 1 software.The OR value and confidence interval (CI) were calculated, and the publication bias was assessed by Begg test and Egger test.Results There was significant difference between cuplike nuclei morphology appearance and FLT3-ITD mutation (OR =2.59,95 % CI 1.55-4.33,P =0.00).Results from both Begg' s test and Egger’ s test did not show significant difference indicating that there was no publication bias existed.Conclusion The uncommon morphologic variant of AML with cuplike nuclei is highly associated with FLT3-ITD mutation, and the presence of cuplike nuclei in AML represents a distinctive morphologic finding that can be used to prioritize the molecular workup of patients with AML.

  • [1]Chen W,Rassidakis GZ,Li J,et al.High frequency of NPM1 gene mutations in acute myeloid leukemia with prominent nuclear invaginations ("cuplike" nuclei).Blood,2006,108:1783-1784.
  • [2]Kussick SJ, Stirewalt DL, Yi HS, et al. A distinctive nuclear morphology in acute myeloid leukemia is strongly associated with loss of HLA-DR expression and FLT3 internal tandem duplication.Leukemia,2004,18:1591-1598.
  • [3]Kroschinsky FP,Sch(a)kel U,Fischer R,et al.Cup-like acute myeloid leukemia:new disease or artificial phenomenon? Haematologica,2008,93:283-286.
  • [4]Chen W,Konoplev S,Medeiros LJ,et al.Cuplike nuclei (prominent nuclear invaginations) in acute myeloid leukemia are highly associated with FLT3 internal tandem duplication and NPM1 mutation. Cancer,2009,115:5481-5489.
  • [5]McCormick SR,McCormick M J,Grutkoski PS,et al.FLT3 mutations at diagnosis and relapse in acute myeloid leukemia: cytogenetic and pathologic correlations, including cuplike blast morphology. Arch Pathol Lab Med,2010,134:1143-1151.
  • [6]Rakheja D,Konoplev S,Su M,et al.High incidence of IDH mutations in acute myeloid leukaemia with cuplike nuclei.Br J Haematol,2011,doi:10.1111/j.1365-2141.2011.08646.
  • [7]Thiede C, Steudel C, Mohr B, 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.
  • [8]Schnittger S, Schoch C, Dugas M, 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]Preudhomme C, Sagot C, Boissel N, et al. Favorable prognostic significance of CEBPA mutations in patients with de novo acute myeloid leukemia: a study from the acute leukemia french association (ALFA).Blood,2002,100:2717-2723.
  • [10]Mrozek K, Marcucci G, Paschka P, et al. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification? Blood,2007,109:431-448.
  • [11]DeAngelo DJ,Stone RM,Heaney ML,et al.Phase 1 clinical resuits with tandutinib (MLN5 1 8),a novel FLT3 antagonist,in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome:safety,pharmacokinetics and pharmacodynanlies.Blood,2006,108:3674-3681.
  • [12]Knapper S,Burnett AK,Littlewood T,et al.A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy.Blood,2006,108:3262-3270.
  • [13]Safaian NN,Czibere A,Bruns I,et al.Sorafenib (Nexavar) induces molecular remission and regression of extramedullary disease in a patient with FLT3-ITD+ acute myeloid leukemia.Leuk Res,2009,33:348-350.
  • [14]Pratz K, Levis M. Incorporating FLT3 inhibitors into acute myeloid leukemia treatment regimens.Leuk Lymphoma,2008,49:852-863.
  • [15]Mori S,Cortes J,Kantarjian H,et al.Potential role of sorafenib in the treatment of acute myeloid leukemia. Leuk Lymphoma, 2008, 49:2246-2255.
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