Frequency and prognostic value of NPM1 mutations in Sudanese acute myeloid leukemia patients

Eman Ali Elzain; Hiba BadrEldin Khalil

doi:10.30574/gscbps.2021.14.2.0055

Authors

Eman Ali Elzain Department of Haematology, Faculty of Medical laboratory Sciences, International University of Africa, Khartoum, Sudan. ORCID ID: 0000-0002-7797-0369.
Hiba BadrEldin Khalil Hematology and Stem Cell Technology, Al Neelain Stem Cell center, Al Neelain University, Khartoum, Sudan. ORCID ID: 0000-0003-0305-7726.

DOI:

https://doi.org/10.30574/gscbps.2021.14.2.0055

Keywords:

Acute Myeloid Leukemia, NPM1, Sudanese

Abstract

Acute myeloid leukemia (AML) is a malignancy of proliferative, clonal, abnormally differentiated cells of the hematopoietic system, described byevolution and genetic heterogeneity. Molecular genetics of AML regarding the prognosis of patients primarily representing by NPM1. NPM1 is a nucleolar protein that placed on chromosome 5q35.1 which transported between the nucleus and cytoplasm. It is concerned in multiple functions, including ribosomal protein assembly and transport, control of centrosome duplication, and regulation of the tumor suppressor ARF & p53. NPM1 mutations that relocalize NPM1 from the nucleus into the cytoplasm are associated with development of acute myeloid leukemia. The aim of this study was to determine the frequency and shed light on the prognostic value of NPM1 mutations among Sudanese patients with acute myeloid leukemia. A cross sectional study recruited 100 patients in this study clinically diagnosed firstly (not transformed from any other malignancy) as AML patients based on the diagnostic protocol concern radioisotopecentre of Khartoum (RICK) hospital; such as morphological identification, immunophenotyping analysis, and molecular genetics, Of the 100 AML patients, 54% were newly diagnosed and 46% were admitted by chemotherapy treatment and follow up. EDTA blood or bone marrow samples were collected from patients for performing CBC, hematological studies including FAB classification, PCR protocols and sequencing. Genomic DNA was extracted from all samples using guanidine method.

NPM1 mutations detection, sequencing technique was done, then sequencing analysis by software (Mega 7 Software) revealed that there were no NPM1mutations in Sudanese AML patients. The Sudanese AML patients carry wild type NPM1.

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References

Kumar S, Stecher G, Tamura K. MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Molecular biology and evolution. 2016 Mar 22;33(7):1870-4.

Rezaei N, Arandi N, Valibeigi B, Haghpanah S, Khansalar M, Ramzi M. FMS-like tyrosine kinase 3 (FLT3) and nucleophosmin 1 (NPM1) in Iranian adult acute myeloid leukemia patients with normal karyotypes: mutation status and clinical and laboratory characteristics. Turkish Journal of Hematology. 2017 Dec;34(4):300.

Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405.

He R, Oliveira JL, Hoyer JD, Viswanatha DS. Molecular Hematopathology. InHematopathology 2018 Jan 1;712-760.

Wang JA. Cytoplasmic Mislocalization of CTCF by Leukemic Oncogene NPM1c in Acute Myeloid Leukemia. 2019.

Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, Potter NE, Heuser M, Thol F, Bolli N, Gundem G. Genomic classification and prognosis in acute myeloid leukemia. New England Journal of Medicine. 2016 Jun 9;374(23):2209-21.

Uckelmann HJ, Armstrong SA, Stone RM. Location, location, location: Mutant NPM1c cytoplasmic localization is required to maintain stem cell genes in AML. Cancer cell. 2018 Sep 10;34(3):355-7.

Altaybe T. Frequency of AML1: ETO, MLL: AF9, FUS: ERG, and NPM1 gene in Sudanese AML patients. [thesis]. Bahri: Khartoum; 2014.

Dovey OM, Cooper JL, Mupo A, Grove CS, Lynn C, Conte N, Andrews RM, Pacharne S, Tzelepis K, Vijayabaskar MS, Green P. Molecular synergy underlies the co-occurrence patterns and phenotype of NPM1-mutant acute myeloid leukemia. Blood, The Journal of the American Society of Hematology. 2017 Oct 26;130(17):1911-22.

Owaidat HM. Prognostic Value of Day 14 Bone Marrow Morphology in Adult AML patients. CU Theses. 2018.

Gou H, Zhou J, Ye Y, Hu X, Shang M, Zhang J, Zhao Z, Peng W, Zhou Y, Zhou Y, Song X. The prevalence and clinical profiles of FLT3-ITD, FLT3-TKD, NPM1, C-KIT, DNMT3A, and CEBPA mutations in a cohort of patients with de novo acute myeloid leukemia from southwest China. Tumor Biology. 2016 Jun 1;37(6):7357-70.