Int J Lab Hematol. 2020;00:1–8. wileyonlinelibrary.com/journal/ijlh | 1 © 2020 John Wiley & Sons Ltd
1 | INTRODUCTION
Acute myeloid leukemia (AML) with mutated nucleophosmin 1
(NPM1) accounts for approximately one-third of all AML cases.
NPM1 is a nucleocytoplasmic shuttling protein that negatively af-
fects the growth of the mutated cells and offers a good prognosis
in AML. It is commonly associated with high total leukocytic count
(TLC), acute myelomonocytic and acute monocytic leukemia, and
CD34 negativity.
1
Although AML with mutated NPM1 is usually as-
sociated with a normal karyotype, 40% of cases have co-occurring
FMS-like tyrosine kinase internal tandem duplication (FLT3-ITD)
mutations.
2,3
Nucleophosmin mutations were confirmed to confer
a favorable prognostic impact on AML, though various reports were
presented as how the presence of other mutations, for example,
FLT3-ITD, DNMT3A, and IDH1/2 mutations, may negatively affect
the good prognosis of NPM1 mutations.
4-8
Hence, "AML with mu-
tated NPM1" has been included as a provisional entity in the WHO
classification of tumors of hematopoietic and lymphoid tissues.
1
About 50 variants of NPM1 mutations have been identified in
AML. Almost all these mutations are in exon 12, in a mutational hot
Received: 6 May 2020
|
Revised: 18 July 2020
|
Accepted: 29 July 2020
DOI: 10.1111/ijlh.13317
ORIGINAL ARTICLE
Flow cytometry in detection of Nucleophosmin 1 mutation
in acute myeloid leukemia patients: A reproducible tertiary
hospital experience
Rasha Abd El-Rahman El-Gamal | Azza El-Sayed Hashem |
Deena Mohamed Habashy | Menna Allah Zakareya Abou Elwafa |
Noha Hussein Boshnak
Department of Clinical Pathology,
Hematology Unit, Ain Shams University,
Cairo, Egypt
Correspondence
Rasha Abd El-Rahman El-Gamal, Clinical
Pathology Department, Faculty of Medicine,
Ain Shams University, Abbasseya, Cairo,
11566, Egypt.
Email: rashaelgamal@hotmail.com
Funding information
Faculty of medicine Grants office, Grant/
Award Number: 2017/22
Abstract
Introduction: Nucleophosmin 1 (NPM1) mutation is one of the most frequent gene
mutations in adult acute myeloid leukemia (AML), being detected in 35% of all cases
and in up to 60% of patients with normal karyotype AML. AML with mutated NPM1
has distinct pathology, immunophenotyping, and confirmed favorable prognostic sig-
nificance. Hence, AML with mutated NPM1 is a separate entity in the revised 2016
World Health Organization classification. This study aimed to evaluate the use of a
reproducible flow cytometry approach in the assay of mutant NPM1 protein in AML
patients and to correlate flow cytometric results with the NPM1 gene mutation.
Methods: Eighty-nine newly diagnosed AML patients were evaluated for the expres-
sion of mutant NPM1 using flow cytometry and for the presence of NPM1 exon 12
mutations using high-resolution melting polymerase chain reaction (HRM PCR).
Results: The NPM1 mutation was found in 35 (39.3%) patients by HRM PCR. These
patients showed a significantly higher level of percentage of positive-stained cells (%
positive cells) and normalized median fluorescence intensity (MFI) for mutant NPM1
by flow cytometry than the negative mutation group.
Conclusion: Flow cytometric detection of mutant NPM1 offers a possible tool to
indicate NPM1 mutational status.
KEYWORDS
acute myeloid leukemia, flow cytometry, HRM PCR, NPM1