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Identification of NPMc+ acute myeloid leukemia in bone marrow smears
Judit Bedekovics1, László Rejtő, Béla Telek
1Department of Pathology, University of Debrecen, Debrecen, Hungary.
Abstract:
The most frequent genetic change currently known in acute myeloid leukemia (AML) is the mutation of the nucleophosmin (NPM) gene. Aberrant cytoplasmic accumulation of NPM protein (NPMc+) is the result of this mutation, and it can be demonstrated by immunohistochemistry for the identification of a favorable subgroup within "AML with normal karyotype" according to the World Health Organization classification. NPM staining pattern was defined in 71 AML and 15 control cases by the use of bone marrow smears in order to overcome limitations observed due to immunohistochemistry. In 13/71 cases (18.3%), clear cytoplasmic staining of the leukemic blast cells was detectable that was comparable with the positivity of mitotic figures physiologically lacking nuclear membrane. The biological and genetic characteristics of the NPMc+ cases determined this way were identical with the previously published results including low CD34 and HLA-DR expression and lack of recurrent karyotype abnormalities. Bone marrow smears are well applicable and therefore a real alternative for the determination of NPM with the highest accuracy for optimal risk stratification in AML.
Insights
Nucleophosmin (NPM) gene mutations are common in acute myeloid leukemia (AML). Bone marrow smear analysis accurately identifies NPM cytoplasmic accumulation (NPMc+), aiding risk stratification in AML patients.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Nucleophosmin (NPM) gene mutations are the most frequent genetic alteration in acute myeloid leukemia (AML).
- Aberrant cytoplasmic accumulation of NPM protein (NPMc+) results from these mutations and identifies a favorable subgroup in "AML with normal karyotype" (WHO classification).
- Immunohistochemistry (IHC) is used for NPMc+ detection, but limitations exist.
Purpose of the Study:
- To evaluate bone marrow smears as an alternative method for determining NPM staining patterns in AML.
- To assess the diagnostic accuracy and applicability of bone marrow smears for NPMc+ detection.
- To correlate NPMc+ status with biological and genetic characteristics for risk stratification.
Main Methods:
- Bone marrow smears were analyzed for NPM staining patterns in 71 AML cases and 15 controls.
- Cytoplasmic staining of leukemic blast cells was assessed and compared to IHC findings.
- Biological and genetic characteristics (CD34, HLA-DR expression, karyotype abnormalities) of NPMc+ cases were analyzed.
Main Results:
- Clear cytoplasmic NPM staining (NPMc+) was detected in 18.3% (13/71) of AML cases using bone marrow smears.
- The NPM staining pattern observed in smears was comparable to positive mitotic figures.
- NPMc+ cases exhibited biological and genetic profiles consistent with previous studies, including low CD34/HLA-DR and lack of recurrent karyotype abnormalities.
Conclusions:
- Bone marrow smears are a highly accurate and applicable method for determining NPM status in AML.
- This technique offers a viable alternative to IHC for NPMc+ detection.
- Accurate NPM status determination via bone marrow smears facilitates optimal risk stratification in AML.
