| Peer-Reviewed

Molecular Study of NPM1-A (Nucleophosmin1-A) Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters

Received: 3 March 2017     Accepted: 20 March 2017     Published: 19 April 2017
Views:       Downloads:
Abstract

Acute myeloid leukemia (AML) is a hematological malignancy of myeloid progenitor cells characterized by anomalous proliferation, inhibition of differentiation and expansion of leukemic cells blocked at the early stage of hematopoiesis. The molecular markers have become a smart tool to further division of AML patients into subgroups. Nucleophosmin (NPM1) mutations are found in approximately 30% of adult AML patients and are associated with a favorable outcome when detected in absence of FLT3-ITD mutation. Over 50 molecular NPM1 mutation variants have been identified; the most common one is NPM1-A mutation. The current study aims to detect; the frequency of NPM1-A in Iraqi adult newly diagnosed AML patients using real time – PCR technique and evaluate the relationship of NPM1-A with age, gender, total white blood cell (WBC) count and FAB subtypes of the disease. The frequency of NPM1-A mutation in newly diagnosed AML patients was 18.86%. Age was non-significantly higher in NPM1-A mutated patients than in patients without mutation (P=0.538). The NPM1-A mutation was predominantly seen in male (P= 0.069). The mutation was non-significantly higher among monocytic subtypes (M5+M4) compared with the other subtypes of the disease (P=0.916). In the NPM1 mutated group, the total WBC count was non-significantly higher than the non-mutated group (P=0.302). These findings suggest; Real time-PCR technique using TaqMan probe was very specific molecular test for this mutation. Mutated NPM1-A patients were associated with increased age, a higher total WBC count, male predominance and the monocytic subtypes of the disease.

Published in American Journal of Internal Medicine (Volume 5, Issue 3)
DOI 10.11648/j.ajim.20170503.11
Page(s) 37-40
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2017. Published by Science Publishing Group

Keywords

Acute Myeloid Leukemia, NPM1-A, Real Time-PCR

References
[1] Charles A Schiffer, John Anastasi. Clinical manifestations, pathologic features, and diagnosis of acute myeloid leukemia. Up To Date: Jan 21, 2015.
[2] Visser O, Trama A, Maynadie M, Stiller C, Marcos-Gragera R, De Angelis R, Mallone S, Tereanu C, Allemani C, Ricardi U, Schouten HC. Incidence, survival and prevalence of myeloid malignancies in Europe. European Journal of Cancer. 2012 Nov 30; 48 (17):3257-66.
[3] Hou HA, Tien HF, Chou WC. Genetic Alterations and Their Clinical Implications in Acute Myeloid Leukemia. INTECH Open Access Publisher; 2011.
[4] Thiede C, et al. Different types of NPM1 mutations in children and adults: evidence for an effect of patient age on the prevalence of the TCTG-tandem duplication in NPM1-exon12. Leukemia (2007) 21:366–7.
[5] Braoudaki M, et al. The frequency of NPM1 mutations in child- hood acute myeloid leukemia. J HematolOncol (2010) 3:41.
[6] Arber D. A, et al. Acute myeloid leukemia (AML) and related precursor neoplasms. In: Swerdlow S. H, et al, eds. WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. Vol 4. Lyon, France: International Agency for Research on Cancer (IARC); 920(08) 110-123.
[7] Falini, B., et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med (2005) 352, 254-266.
[8] Falini, B., et al. Acute m\yeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity? Blood (2011) 117, 1109-1120.
[9] Boissel, N., et al. Prevalence, clinical profile, and prognosis of NPM mutations in AML with normal karyotype. Blood (2005) 106, 3618-3620.
[10] Bennett JM, Catovsky D, Daniel M-T, et al. Criteria for the diagnosis of acute leukemia of megakaryocytic lineage (M7): a report ofthe French-American-British cooperative group. Ann Intern Med 1985; 103:460-2.
[11] Al-Husseinawi EK. A surrogate marker to detect nucleophosnim (NPM1) gene mutations in the cytoplasm of acute myeloid leukemia (AML) blast cells in 30 adult Iraqi patients. Annals of Saudi medicine. 2013 Nov 1; 33 (6):539.
[12] Dhahir EK, Dhahi MA. High frequency of nucleophosmin mutations in thirty two Iraqi adult patients with acute myeloid leukemia. International Journal of Applied. 2012 May; 2 (5).
[13] Al-Husseinawi EK. Molecular Detection of Type A Nucleophosmin Mutation for the First Time in Forty Four Iraqi Patients with AML: Correlation with prognosis. International Journal of Applied. 2013 Mar; 3 (3).
[14] Pazhakh V, Zaker F, Alimoghaddam K, Atashrazm F. Detection of nucleophosmin and FMS-like tyrosine kinase-3 gene mutations in acute myeloid leukemia. Annals of Saudi medicine. 2011 Jan; 31 (1):45.
[15] Rau R, Brown P. Nucleophosmin (NPM1) mutations in adult and childhood acute myeloid leukaemia: towards definition of a new leukaemia entity. Hematological oncology. 2009 Dec 1; 27 (4):171-81.
[16] Thiede C, Creutzig E, Illmer T, Schaich M, Heise V, Ehninger G, Landt O. Rapid and sensitive typing of NPM1 mutations using LNA-mediated PCR clamping. Leukemia. 2006 Oct 1; 20 (10):1897-9.
[17] Falini B, Martelli MP, Pileri SA, Mecucci C. Molecular and alternative methods for diagnosis of acute myeloid leukemia with mutated NPM1: flexibility may help. Haematologica. 2010 Apr 1; 95 (4):529-34.
[18] Kassem N, Hamid AA, Attia T, Baathallah S, Mahmoud S, Moemen E, Safwat E, Khalaf M, Shaker O. Novel mutations of the nucleophosmin (NPM-1) gene in Egyptian patients with acute myeloid leukemia: A pilot study. Journal of the Egyptian National Cancer Institute. 2011 Jun 30; 23 (2):73-8.
[19] Nafea D, Rahman MA, Boris D, Perot C, Laporte JP, Isnard F, Coppo P, Gorin NC. Incidence and prognostic value of NPM1 and FLT3 gene mutations in AML with normal karyotype. Open Hematology Journal. 2011; 5:14-20.
[20] Verhaak RG, Goudswaard CS, van Putten W, Bijl MA, Sanders MA, Hugens W, Uitterlinden AG, Erpelinck CA, Delwel R, Löwenberg B, Valk PJ. Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance. Blood. 2005 Dec 1; 106 (12):3747-54.
[21] Döhner K, Schlenk RF, Habdank M, Scholl C, Rücker FG, Corbacioglu A, Bullinger L, Fröhling S, Döhner H. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood. 2005 Dec 1; 106 (12):3740-6.
[22] Wang L, Xu WL, Meng HT, Qian WB, Mai WY, Tong HY, Mao LP, Tong Y, Qian JJ, Lou YJ, Chen ZM. FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics. Journal of Zhejiang University Science B. 2010 Oct 1; 11 (10):762-70.
[23] Chen W, Rassidakis GZ, Medeiros LJ. Nucleophosmin gene mutations in acute myeloid leukemia. Archives of pathology & laboratory medicine. 2006 Nov; 130 (11):1687-92.
Cite This Article
  • APA Style

    Shaymaa Abdulateef, Ali Almothaffar, Khitam Razzak Al-khafaji. (2017). Molecular Study of NPM1-A (Nucleophosmin1-A) Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters. American Journal of Internal Medicine, 5(3), 37-40. https://doi.org/10.11648/j.ajim.20170503.11

    Copy | Download

    ACS Style

    Shaymaa Abdulateef; Ali Almothaffar; Khitam Razzak Al-khafaji. Molecular Study of NPM1-A (Nucleophosmin1-A) Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters. Am. J. Intern. Med. 2017, 5(3), 37-40. doi: 10.11648/j.ajim.20170503.11

    Copy | Download

    AMA Style

    Shaymaa Abdulateef, Ali Almothaffar, Khitam Razzak Al-khafaji. Molecular Study of NPM1-A (Nucleophosmin1-A) Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters. Am J Intern Med. 2017;5(3):37-40. doi: 10.11648/j.ajim.20170503.11

    Copy | Download

  • @article{10.11648/j.ajim.20170503.11,
      author = {Shaymaa Abdulateef and Ali Almothaffar and Khitam Razzak Al-khafaji},
      title = {Molecular Study of NPM1-A (Nucleophosmin1-A) Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters},
      journal = {American Journal of Internal Medicine},
      volume = {5},
      number = {3},
      pages = {37-40},
      doi = {10.11648/j.ajim.20170503.11},
      url = {https://doi.org/10.11648/j.ajim.20170503.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20170503.11},
      abstract = {Acute myeloid leukemia (AML) is a hematological malignancy of myeloid progenitor cells characterized by anomalous proliferation, inhibition of differentiation and expansion of leukemic cells blocked at the early stage of hematopoiesis. The molecular markers have become a smart tool to further division of AML patients into subgroups. Nucleophosmin (NPM1) mutations are found in approximately 30% of adult AML patients and are associated with a favorable outcome when detected in absence of FLT3-ITD mutation. Over 50 molecular NPM1 mutation variants have been identified; the most common one is NPM1-A mutation. The current study aims to detect; the frequency of NPM1-A in Iraqi adult newly diagnosed AML patients using real time – PCR technique and evaluate the relationship of NPM1-A with age, gender, total white blood cell (WBC) count and FAB subtypes of the disease. The frequency of NPM1-A mutation in newly diagnosed AML patients was 18.86%. Age was non-significantly higher in NPM1-A mutated patients than in patients without mutation (P=0.538). The NPM1-A mutation was predominantly seen in male (P= 0.069). The mutation was non-significantly higher among monocytic subtypes (M5+M4) compared with the other subtypes of the disease (P=0.916). In the NPM1 mutated group, the total WBC count was non-significantly higher than the non-mutated group (P=0.302). These findings suggest; Real time-PCR technique using TaqMan probe was very specific molecular test for this mutation. Mutated NPM1-A patients were associated with increased age, a higher total WBC count, male predominance and the monocytic subtypes of the disease.},
     year = {2017}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Molecular Study of NPM1-A (Nucleophosmin1-A) Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters
    AU  - Shaymaa Abdulateef
    AU  - Ali Almothaffar
    AU  - Khitam Razzak Al-khafaji
    Y1  - 2017/04/19
    PY  - 2017
    N1  - https://doi.org/10.11648/j.ajim.20170503.11
    DO  - 10.11648/j.ajim.20170503.11
    T2  - American Journal of Internal Medicine
    JF  - American Journal of Internal Medicine
    JO  - American Journal of Internal Medicine
    SP  - 37
    EP  - 40
    PB  - Science Publishing Group
    SN  - 2330-4324
    UR  - https://doi.org/10.11648/j.ajim.20170503.11
    AB  - Acute myeloid leukemia (AML) is a hematological malignancy of myeloid progenitor cells characterized by anomalous proliferation, inhibition of differentiation and expansion of leukemic cells blocked at the early stage of hematopoiesis. The molecular markers have become a smart tool to further division of AML patients into subgroups. Nucleophosmin (NPM1) mutations are found in approximately 30% of adult AML patients and are associated with a favorable outcome when detected in absence of FLT3-ITD mutation. Over 50 molecular NPM1 mutation variants have been identified; the most common one is NPM1-A mutation. The current study aims to detect; the frequency of NPM1-A in Iraqi adult newly diagnosed AML patients using real time – PCR technique and evaluate the relationship of NPM1-A with age, gender, total white blood cell (WBC) count and FAB subtypes of the disease. The frequency of NPM1-A mutation in newly diagnosed AML patients was 18.86%. Age was non-significantly higher in NPM1-A mutated patients than in patients without mutation (P=0.538). The NPM1-A mutation was predominantly seen in male (P= 0.069). The mutation was non-significantly higher among monocytic subtypes (M5+M4) compared with the other subtypes of the disease (P=0.916). In the NPM1 mutated group, the total WBC count was non-significantly higher than the non-mutated group (P=0.302). These findings suggest; Real time-PCR technique using TaqMan probe was very specific molecular test for this mutation. Mutated NPM1-A patients were associated with increased age, a higher total WBC count, male predominance and the monocytic subtypes of the disease.
    VL  - 5
    IS  - 3
    ER  - 

    Copy | Download

Author Information
  • Baquba Teaching Hospital, Diyala, Iraq

  • Department of Medicine, University of Baghdad, Baghdad, Iraq

  • Department of Pathology and Forensic Medicine, University of Baghdad, Baghdad, Iraq

  • Sections