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Morphology

A distinctive nuclear morphology in acute myeloid leukemia is strongly associated with loss of HLA-DR expression and FLT3 internal tandem duplication

Leukemia volume 18, pages 1591–1598 (2004)Cite this article

Abstract

In a 5-year survey of nonpromyelocytic/nonmonocytic acute myeloid leukemias (AMLs) diagnosed in the University of Washington Hematopathology Laboratory, we identified 19 cases containing distinctive, cup-like nuclear indentation in 10% or more of the blasts (‘AML-cuplike’). Fourteen of these cases (74%) demonstrated near-complete loss of HLA-DR expression, while the other five cases showed partial loss of HLA-DR. A total of 16 of the cases (84%) demonstrated internal tandem duplication (ITD) of the Flt3 gene. When compared to a selected set of AMLs lacking this nuclear morphology, AML-cuplike was significantly more likely to lack HLA-DR and CD34 expression, to express CD123 without CD133, to have a normal karyotype, and to harbor the Flt3 ITD. To characterize AML-cuplike in an unselected series of AMLs, we analyzed 42 consecutive nonpromyelocytic/nonmonocytic AMLs diagnosed in our laboratory during a 6-month period in 2002. Strikingly, in this unselected series, there was a statistically significant coincidence of invaginated nuclear morphology, loss of HLA-DR, and presence of the Flt3 ITD beyond that expected if these three features were unrelated, suggesting that AMLs with these three features may represent a distinct AML subset.

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Acknowledgements

We thank the technical staff of the University of Washington Hematopathology Laboratory for outstanding help in the flow cytometric evaluation of all the cases in this series, and for the cryopreservation and maintenance of a number of the cases in this series. We thank the technical staff of the University of Washington Molecular Hematology Laboratory for assistance in developing the FLT3 ITD assay on the ABI 310. We thank Dr Tony Rossini of the University of Washington Department of Medical Education and Biomedical Informatics for statistical advice.This study was supported by grants K23 CA92405 and CA18029 from the National Institutes of Health and National Cancer Institute.

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Authors and Affiliations

  1. Department of Laboratory Medicine, University of Washington, Seattle, WA, USA

    S J Kussick, H S Yi & B L Wood

  2. The Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    D L Stirewalt, K M Sheets, E Pogosova-Agadjanyan & J P Radich

  3. Department of Pathology, University of Washington, Seattle, WA, USA

    S Braswell & T H Norwood

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  1. S J Kussick
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  2. D L Stirewalt
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  3. H S Yi
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  9. B L Wood
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Correspondence to S J Kussick.

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Kussick, S., Stirewalt, D., Yi, H. 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 18, 1591–1598 (2004). https://doi.org/10.1038/sj.leu.2403458

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  • DOI: https://doi.org/10.1038/sj.leu.2403458

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