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Review
. 2024 Jan 8;5(1):8-20.
doi: 10.1158/2643-3230.BCD-23-0144.

Criteria for Diagnosis and Molecular Monitoring of NPM1-Mutated AML

Brunangelo Falini  1 , Richard Dillon  2
Affiliations
Review

Criteria for Diagnosis and Molecular Monitoring of NPM1-Mutated AML

Brunangelo Falini et al. Blood Cancer Discov. .

Abstract

NPM1-mutated acute myeloid leukemia (AML) represents the largest molecular subgroup of adult AML. NPM1-mutated AML is recognizable by molecular techniques and immunohistochemistry, which, when combined, can solve difficult diagnostic problems (including identification of myeloid sarcoma and NPM1 mutations outside exon 12). According to updated 2022 European LeukemiaNet (ELN) guidelines, determining the mutational status of NPM1 (and FLT3) is a mandatory step for the genetic-based risk stratification of AML. Monitoring of measurable residual disease (MRD) by qRT-PCR, combined with ELN risk stratification, can guide therapeutic decisions at the post-remission stage. Here, we review the criteria for appropriate diagnosis and molecular monitoring of NPM1-mutated AML.

Significance: NPM1-mutated AML represents a distinct entity in the 2022 International Consensus Classification and 5th edition of World Health Organization classifications of myeloid neoplasms. The correct diagnosis of NPM1-mutated AML and its distinction from other AML entities is extremely important because it has clinical implications for the management of AML patients, such as genetic-based risk stratification according to 2022 ELN. Monitoring of MRD by qRT-PCR, combined with ELN risk stratification, can guide therapeutic decisions at the post-remission stage, e.g., whether or not to perform allogeneic hematopoietic stem cell transplantation.

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Figures

Figure 1. Representative examples of subcellular (nuclear and/or cytoplasmic) expression of NPM1 and nucleolin (red staining) in normal tissues, NPM1 wild-type tumors, and NPM1-mutated AML.
Figure 1.
Representative examples of subcellular (nuclear and/or cytoplasmic) expression of NPM1 and nucleolin (red staining) in normal tissues, NPM1 wild-type tumors, and NPM1-mutated AML.
Figure 2. NPM1-mutated myeloid sarcoma (lymph node). A, Partial infiltration of the lymph node (asterisk) by leukemic cells showing aberrant cytoplasmic expression of nucleophosmin (brown; immunoperoxidase; hematoxylin counterstaining; × 100. B, The same field showing NPM1 cytoplasmic positive tumor cells at higher magnification (immunoperoxidase; hematoxylin counterstaining; × 400).
Figure 2.
NPM1-mutated myeloid sarcoma (lymph node). A, Partial infiltration of the lymph node (asterisk) by leukemic cells showing aberrant cytoplasmic expression of nucleophosmin (brown; immunoperoxidase; hematoxylin counterstaining; × 100. B, The same field showing NPM1 cytoplasmic positive tumor cells at higher magnification (immunoperoxidase; hematoxylin counterstaining; × 400).
Figure 3. IHC and molecular procedure for recognizing NPM1 mutations occurring outside exon 12 and NPM1-containing fusion proteins.
Figure 3.
IHC and molecular procedure for recognizing NPM1 mutations occurring outside exon 12 and NPM1-containing fusion proteins.
Figure 4. Possible approach to the incorporation of MRD into treatment algorithms for patients with NPM1-mutated AML.
Figure 4.
Possible approach to the incorporation of MRD into treatment algorithms for patients with NPM1-mutated AML.
See this image and copyright information in PMC

References

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