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

Kussick, Steven J.; Stirewalt, Derek L.; Yi, Hye Son; Sheets, Kayla M.; Pogosova-Agadjanyan, Era L.; Braswell, Scott; Norwood, Thomas H.; Radich, Jerald P.; Wood, Brent L.

doi:10.1038/sj.leu.2403458

Cited by 76 publications

(61 citation statements)

References 20 publications

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“…Therefore we used a cut-off of ≥5% blast cells with typical morphology in blood and/or bone marrow for the definition of cup-like AML for the statistical analyses, which was lower than in the studies by Kussik et al 2 and Chen et al 3 The phenomenon seemed to be more pronounced in the peripheral blood and this was in line with the higher median percentage of cup-like positive blast cells in this group. Whether there really are more cup-like cells in the PB, or whether the phenomenon is induced by preparing the smears, remains hypothetical.…”

Section: Resultsmentioning

confidence: 71%

Cup-like acute myeloid leukemia: new disease or artificial phenomenon?

Kroschinsky

Schäkel²,

Fischer³

et al. 2008

Haematologica

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We investigated cup-like nuclear morphology of acute myeloid leukemia blasts in 266 randomly selected patients and its association with hematologic findings, disease markers and outcome data. Cup-like acute myeloid leukemia was diagnosed in 55 patients (21%). It was associated with female sex, high white blood cell and blast cell counts, normal karyotype, and low CD34 and HLA-DR expression. Mutations of FLT3, NPM1 or both were detected in 84.9% compared with 58.1% in cases without this morphology (p=0.001). There was no influence on response to treatment or survival. Therefore, cup-like nuclear morphology is an indicator of normal karyotype and should guide more specific molecular analyses.

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Section: Resultsmentioning

confidence: 71%

Cup-like acute myeloid leukemia: new disease or artificial phenomenon?

Kroschinsky

Schäkel²,

Fischer³

et al. 2008

Haematologica

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“…The previously described cup-like morphology has been reported to be associated with NPM1 mutations, 4 with FLT3-ITD and with a lack of HLA-DR expression; 10 however, again no complete correlations were observed.…”

Section: Mll-ptdmentioning

confidence: 62%

Flow cytometric identification of acute myeloid leukemia with limited differentiation and NPM1 type A mutation: a new biologically defined entity

et al. 2009

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“…Especially, 10% of non-APL patients were negative for both CD34 and HLA-DR [17]. One author reported that invaginated nuclear morphology was associated with loss of HLA-DR and CD34 expressions in non-APL [19]. These results suggested that absence of HLA-DR antigen was accompanied by absence of CD34 antigen in AML.…”

Section: Disussionmentioning

confidence: 66%

Characteristics of Acute Myeloid Leukemia without HLA-DR Expression

et al. 2007

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Immunophenotype is one of the most useful tool for the identification of leukemia subtypes [1][2][3][4][5] and can be assigned within a few hours after bone marrow sampling.The typical immunophenotypic feature of acute promyelocytic leukemia (APL) has been reported as CD34-, HLA-DR-, CD13+, and CD33+ [6][7][8]. It has been reported that HLA-DR antigens are consistently negative in APL, whereas the majority of non-APL cases are positive for HLA-DR expression [9,10]; therefore, HLA-DR negativity is known to be useful for distinguishing APL from other AML subtypes, even before the PML-RARA gene rearrangement is identified by cytogenetic or molecular stud- Background : HLA-DR negativity is known to be useful for distinguishing acute promyelocytic leukemia (APL) from other subtypes of AML, but non-APL cases without HLA-DR antigen expression have been reported. The purpose of this study was to evaluate and compare the characteristics of APL, HLA-DR negative non-APL, and HLA-DR positive non-APL cases.Methods : A total of 114 cases of AML admitted at Ewha Womans University, Mokdong Hospital between March 1997 and June 2006 were included in this study. A diagnosis of AML was made based on the results of morphology, cytochemistry, immunophenotype, cytogenetics, and/or fluorescence in situ hybridization.Results : Among the 114 AML patients, HLA-DR antigen was not expressed in 39 (34%), including 24 non-APL (62%) and 15 APL patients (38%). The HLA-DR negative non-APL group showed higher leukocyte counts and positive rate of CD19 expression than did APL group (P<0.05). The remaining laboratory findings were not statistically different between the HLA-DR negative non-APL and APL groups. CD34 expression was more frequent in the HLA-DR positive non-APL group than in the HLA-DR negative non-APL group and APL group. Of the 24 patients with HLA-DR negative non-APL, 7 patients had disseminated intravascular coagulation and 2 patients showed morphologic features similar to those of APL.Conclusions : CD19 expression and leukocyte count may be helpful for differentiating HLA-DR negative non-APL from APL. However, the final diagnosis and classification should be confirmed by cytogenetic or molecular studies. (Korean J Lab Med 2007;27:313-7)

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

Cited by 76 publications

References 20 publications

Cup-like acute myeloid leukemia: new disease or artificial phenomenon?

Cup-like acute myeloid leukemia: new disease or artificial phenomenon?

Flow cytometric identification of acute myeloid leukemia with limited differentiation and NPM1 type A mutation: a new biologically defined entity

Characteristics of Acute Myeloid Leukemia without HLA-DR Expression

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