Annals of Hematology

, Volume 92, Issue 4, pp 451–457 | Cite as

Association of cup-like nuclei in blasts with FLT3 and NPM1 mutations in acute myeloid leukemia

  • Borae G. Park
  • Hyun-Sook Chi
  • Seongsoo Jang
  • Chan-Jeoung Park
  • Dae-Young Kim
  • Jung-Hee Lee
  • Je-Hwan Lee
  • Kyoo-Hyung Lee
Original Article


The purpose of this study was to investigate the correlation of mutations of the fms-like tyrosine kinase (FLT3) and nucleophosmin (NPM1) genes with the cup-like nuclear morphology of blasts in patients with acute myeloid leukemia (AML). We retrospectively reviewed peripheral blood (PB) and bone marrow (BM) slides of 208 patients prepared at the time of diagnosis of AML based on the results of testing for mutations of both NPM1 exon 12 and FLT3. We investigated the association between this phenotype and hematologic findings, disease markers, and mutations in NPM1 exon 12, FLT3-internal tandem duplication (ITD), and tyrosine kinase domain (TKD) genes. Cup-like nuclei were found in 44 patients (21.2 %) diagnosed with AML. This morphology was associated with high blast counts in the PB and BM; AML type, especially AML M1 (FAB classification); low CD34 expression; and mutation of FLT3-ITD, -TKD, NPM1 regardless of other mutations (p < 0.05 for all). However, FLT3-ITD or TKD mutation alone (nine cases, p = 0.228) was not associated, and NPM1 mutation alone (14 cases, p = 0.036) was weakly associated with cup-like nuclei. Mutation of both NPM1 and FLT3-ITD or TKD (17 cases, p < 0.001) was strongly correlated with the cup-like nuclear morphology. AML with cup-like nuclei is strongly associated with co-occurring mutations of both NPM1 and FLT3-ITD or TKD. Therefore, testing for both mutations is recommended for patients with the cup-like nuclear morphology.


Cup-like nuclei Acute myeloid leukemia NPM1 FLT3 


Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Borae G. Park
    • 1
  • Hyun-Sook Chi
    • 1
  • Seongsoo Jang
    • 1
  • Chan-Jeoung Park
    • 1
  • Dae-Young Kim
    • 2
  • Jung-Hee Lee
    • 2
  • Je-Hwan Lee
    • 2
  • Kyoo-Hyung Lee
    • 2
  1. 1.Department of Laboratory MedicineUniversity of Ulsan College of Medicine and Asan Medical CenterSeoulSouth Korea
  2. 2.Department of Internal Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea

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