Molecular Study of FLT3-ITD Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters

Shaymaa Abdulateef; Ali Almothaffar; Khitam Razzak Al-khafaji

doi:doi:10.11648/j.plm.20170101.13

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Molecular Study of FLT3-ITD Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters

Shaymaa Abdulateef, Ali Almothaffar, Khitam Razzak Al-khafaji

Published in Pathology and Laboratory Medicine (Volume 1, Issue 1)

Received: 3 March 2017 Accepted: 21 March 2017 Published: 19 April 2017

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Abstract

Acute myeloid leukemia (AML) is a hematological malignancy of myeloid progenitor cells characterized by abnormal proliferation, inhibition of differentiation and expansion of leukemic cells prevented at the early step of hematopoiesis. Detection of molecular markers has become a smart tool to further division of patients in AML subgroups. The Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations are found in about 20-25% of AML patients and it is associated with increased transcript level of FLT3 and with unfortunate prognosis in adult AML patients. This study aims to find FLT3-ITD mutation in Iraqi adult newly diagnosed AML patients using real time-PCR technique and gel electrophoresis post PCR procedure as well as to evaluate the relationship of FLT3-ITD mutation with clinicopathological parameters including age, gender, total WBC count and FAB subtypes of the disease. FLT3-ITD mutation was found in 1.88% of AML patients. FLT3-ITD mutation was not related to any clinical variables including age, gender, total WBC count and FAB subtypes of the disease with statistical significance. These findings suggest low rate of FLT3-ITD is found in Iraqi adult AML patients and no correlations are established between FLT3-ITD mutation and any clinical variables of AML including age, gender, total WBC count and FAB subtypes of the disease.

Published in	Pathology and Laboratory Medicine (Volume 1, Issue 1)
DOI	10.11648/j.plm.20170101.13
Page(s)	14-17
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, FLT3-ITD, Real Time- PCR

References

[1]	NCCN Guidelines Version 2.2014: Acute Myeloid Leukemia. www.nccn.org. Accessed14 September 2014.
[2]	American Cancer Society. Leukemia- Acute Myeloid (Myelogenous) Overview. Available at: http://www.cancer.org/cancer/leukemia-acutemyeloidaml/overviewguide/leukemia-aml-overview-what-is-aml (accessed: October 2014).
[3]	Hou HA, Tien HF, Chou WC. Genetic Alterations and Their Clinical Implications in Acute Myeloid Leukemia. INTECH Open Access Publisher; 2011.
[4]	Abu‐Duhier FM, Goodeve AC, Wilson GA, Gari MA, Peake IR, Rees DC, Vandenberghe EA, Winship PR, Reilly JT. FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high‐risk group. British journal of haematology. 2000 Oct 1; 111(1): 190-5.
[5]	Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA, Walker H, Wheatley K, Bowen DT, Burnett AK, Goldstone AH. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001 Sep 15; 98(6): 1752-9.
[6]	Gale RE, Green C, Allen C, Mead AJ, Burnett AK, Hills RK, Linch DC. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood. 2008 Mar 1; 111(5): 2776-84.
[7]	Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, Habdank M, Späth D, Morgan M, Benner A, Schlegelberger B. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. New England Journal of Medicine. 2008 May 1; 358(18): 1909-18.
[8]	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.
[9]	Dhahir EK, Al-Mudallel SS, Dhahi MA. The frequency of FLT3 mutation in fifty-five Iraqi adult patients with acute myeloid leukemia. Iraqi Journal of Medical Sciences. 2012: 140.
[10]	Kiyoi H, Towatari M, Yokota S, Hamaguchi M, Ohno R, Saito H, Naoe T. Internal tandem duplication of the FLT3 gene is a novel modality of elongation mutation which causes constitutive activation of the product. Leukemia (08876924). 1998 Sep 1; 12 (9).
[11]	Auewarakul CU, Sritana N, Limwongse C, Thongnoppakhun W, Yenchitsomanus PT. Mutations of the FLT3 gene in adult acute myeloid leukemia: determination of incidence and identification of a novel mutation in a Thai population. Cancer genetics and cytogenetics. 2005 Oct 15; 162(2): 127-34.
[12]	Wang L, Lin D, Zhang X, Chen S, Wang M, Wang J. Analysis of FLT3 internal tandem duplication and D835 mutations in Chinese acute leukemia patients. Leukemia research. 2005 Dec 31; 29(12): 1393-8.
[13]	Thiede C, Steudel C, Mohr B, Schaich M, Schäkel U, Platzbecker U, Wermke M, Bornhäuser M, Ritter M, Neubauer A, Ehninger G. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. 2002 Jun 15; 99 (12): 4326-35.
[14]	Gari M, Abuzenadah A, Chaudhary A, Al-Qahtani M, Banni H, Ahmad W, Al-Sayes F, Lary S, Damanhouri G. Detection of FLT3 oncogene mutations in acute myeloid leukemia using conformation sensitive gel electrophoresis. International journal of molecular sciences. 2008 Nov 11;9(11): 2194-204.
[15]	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.
[16]	Bang SM, Ahn JY, Park J, Park SH, Park J, Cho EK, Shin DB, Lee JH, Yoo SJ, Jeon IS, Kim YK. Low frequency and variability of FLT3 mutations in Korean patients with acute myeloid leukemia. Journal of Korean medical science. 2008 Oct 1; 23(5): 833-7.
[17]	Fenski R, Flesch K, Serve S, Mizuki M, Oelmann E, Kratz A, Kienast J, Leo R, Schwartz S, Berdel WE, Serve H. Constitutive activation of FLT3 in acute myeloid leukaemia and its consequences for growth of 32D cells. Br. J. Haematol. 2000; 108: 322–330.
[18]	Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA, Walker H, Wheatley K, Bowen DT, Burnett AK, Goldstone AH. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001 Sep 15; 98(6): 1752-9.

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APA Style

Shaymaa Abdulateef, Ali Almothaffar, Khitam Razzak Al-khafaji. (2017). Molecular Study of FLT3-ITD Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters. Pathology and Laboratory Medicine, 1(1), 14-17. https://doi.org/10.11648/j.plm.20170101.13

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ACS Style

Shaymaa Abdulateef; Ali Almothaffar; Khitam Razzak Al-khafaji. Molecular Study of FLT3-ITD Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters. Pathol. Lab. Med. 2017, 1(1), 14-17. doi: 10.11648/j.plm.20170101.13

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AMA Style

Shaymaa Abdulateef, Ali Almothaffar, Khitam Razzak Al-khafaji. Molecular Study of FLT3-ITD Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters. Pathol Lab Med. 2017;1(1):14-17. doi: 10.11648/j.plm.20170101.13

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@article{10.11648/j.plm.20170101.13,
  author = {Shaymaa Abdulateef and Ali Almothaffar and Khitam Razzak Al-khafaji},
  title = {Molecular Study of FLT3-ITD Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters},
  journal = {Pathology and Laboratory Medicine},
  volume = {1},
  number = {1},
  pages = {14-17},
  doi = {10.11648/j.plm.20170101.13},
  url = {https://doi.org/10.11648/j.plm.20170101.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.plm.20170101.13},
  abstract = {Acute myeloid leukemia (AML) is a hematological malignancy of myeloid progenitor cells characterized by abnormal proliferation, inhibition of differentiation and expansion of leukemic cells prevented at the early step of hematopoiesis. Detection of molecular markers has become a smart tool to further division of patients in AML subgroups. The Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations are found in about 20-25% of AML patients and it is associated with increased transcript level of FLT3 and with unfortunate prognosis in adult AML patients. This study aims to find FLT3-ITD mutation in Iraqi adult newly diagnosed AML patients using real time-PCR technique and gel electrophoresis post PCR procedure as well as to evaluate the relationship of FLT3-ITD mutation with clinicopathological parameters including age, gender, total WBC count and FAB subtypes of the disease. FLT3-ITD mutation was found in 1.88% of AML patients. FLT3-ITD mutation was not related to any clinical variables including age, gender, total WBC count and FAB subtypes of the disease with statistical significance. These findings suggest low rate of FLT3-ITD is found in Iraqi adult AML patients and no correlations are established between FLT3-ITD mutation and any clinical variables of AML including age, gender, total WBC count and FAB subtypes of the disease.},
 year = {2017}
}

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TY  - JOUR
T1  - Molecular Study of FLT3-ITD 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.plm.20170101.13
DO  - 10.11648/j.plm.20170101.13
T2  - Pathology and Laboratory Medicine
JF  - Pathology and Laboratory Medicine
JO  - Pathology and Laboratory Medicine
SP  - 14
EP  - 17
PB  - Science Publishing Group
SN  - 2640-4478
UR  - https://doi.org/10.11648/j.plm.20170101.13
AB  - Acute myeloid leukemia (AML) is a hematological malignancy of myeloid progenitor cells characterized by abnormal proliferation, inhibition of differentiation and expansion of leukemic cells prevented at the early step of hematopoiesis. Detection of molecular markers has become a smart tool to further division of patients in AML subgroups. The Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations are found in about 20-25% of AML patients and it is associated with increased transcript level of FLT3 and with unfortunate prognosis in adult AML patients. This study aims to find FLT3-ITD mutation in Iraqi adult newly diagnosed AML patients using real time-PCR technique and gel electrophoresis post PCR procedure as well as to evaluate the relationship of FLT3-ITD mutation with clinicopathological parameters including age, gender, total WBC count and FAB subtypes of the disease. FLT3-ITD mutation was found in 1.88% of AML patients. FLT3-ITD mutation was not related to any clinical variables including age, gender, total WBC count and FAB subtypes of the disease with statistical significance. These findings suggest low rate of FLT3-ITD is found in Iraqi adult AML patients and no correlations are established between FLT3-ITD mutation and any clinical variables of AML including age, gender, total WBC count and FAB subtypes of the disease.
VL  - 1
IS  - 1
ER  -

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Author Information

Shaymaa Abdulateef

Baquba Teaching Hospital, Diyala, Iraq
Ali Almothaffar

Medicine Department, College of Medicine, University of Baghdad, Baghdad, Iraq
Khitam Razzak Al-khafaji

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

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APA Style

Shaymaa Abdulateef, Ali Almothaffar, Khitam Razzak Al-khafaji. (2017). Molecular Study of FLT3-ITD Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters. Pathology and Laboratory Medicine, 1(1), 14-17. https://doi.org/10.11648/j.plm.20170101.13

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ACS Style

Shaymaa Abdulateef; Ali Almothaffar; Khitam Razzak Al-khafaji. Molecular Study of FLT3-ITD Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters. Pathol. Lab. Med. 2017, 1(1), 14-17. doi: 10.11648/j.plm.20170101.13

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AMA Style

Shaymaa Abdulateef, Ali Almothaffar, Khitam Razzak Al-khafaji. Molecular Study of FLT3-ITD Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters. Pathol Lab Med. 2017;1(1):14-17. doi: 10.11648/j.plm.20170101.13

Copy | Download

@article{10.11648/j.plm.20170101.13,
  author = {Shaymaa Abdulateef and Ali Almothaffar and Khitam Razzak Al-khafaji},
  title = {Molecular Study of FLT3-ITD Mutation in Iraqi Adult Acute Myeloid Leukemia Patients; Its Correlation with Clinicopathological Parameters},
  journal = {Pathology and Laboratory Medicine},
  volume = {1},
  number = {1},
  pages = {14-17},
  doi = {10.11648/j.plm.20170101.13},
  url = {https://doi.org/10.11648/j.plm.20170101.13},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.plm.20170101.13},
  abstract = {Acute myeloid leukemia (AML) is a hematological malignancy of myeloid progenitor cells characterized by abnormal proliferation, inhibition of differentiation and expansion of leukemic cells prevented at the early step of hematopoiesis. Detection of molecular markers has become a smart tool to further division of patients in AML subgroups. The Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations are found in about 20-25% of AML patients and it is associated with increased transcript level of FLT3 and with unfortunate prognosis in adult AML patients. This study aims to find FLT3-ITD mutation in Iraqi adult newly diagnosed AML patients using real time-PCR technique and gel electrophoresis post PCR procedure as well as to evaluate the relationship of FLT3-ITD mutation with clinicopathological parameters including age, gender, total WBC count and FAB subtypes of the disease. FLT3-ITD mutation was found in 1.88% of AML patients. FLT3-ITD mutation was not related to any clinical variables including age, gender, total WBC count and FAB subtypes of the disease with statistical significance. These findings suggest low rate of FLT3-ITD is found in Iraqi adult AML patients and no correlations are established between FLT3-ITD mutation and any clinical variables of AML including age, gender, total WBC count and FAB subtypes of the disease.},
 year = {2017}
}

Copy | Download

TY  - JOUR
T1  - Molecular Study of FLT3-ITD 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.plm.20170101.13
DO  - 10.11648/j.plm.20170101.13
T2  - Pathology and Laboratory Medicine
JF  - Pathology and Laboratory Medicine
JO  - Pathology and Laboratory Medicine
SP  - 14
EP  - 17
PB  - Science Publishing Group
SN  - 2640-4478
UR  - https://doi.org/10.11648/j.plm.20170101.13
AB  - Acute myeloid leukemia (AML) is a hematological malignancy of myeloid progenitor cells characterized by abnormal proliferation, inhibition of differentiation and expansion of leukemic cells prevented at the early step of hematopoiesis. Detection of molecular markers has become a smart tool to further division of patients in AML subgroups. The Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations are found in about 20-25% of AML patients and it is associated with increased transcript level of FLT3 and with unfortunate prognosis in adult AML patients. This study aims to find FLT3-ITD mutation in Iraqi adult newly diagnosed AML patients using real time-PCR technique and gel electrophoresis post PCR procedure as well as to evaluate the relationship of FLT3-ITD mutation with clinicopathological parameters including age, gender, total WBC count and FAB subtypes of the disease. FLT3-ITD mutation was found in 1.88% of AML patients. FLT3-ITD mutation was not related to any clinical variables including age, gender, total WBC count and FAB subtypes of the disease with statistical significance. These findings suggest low rate of FLT3-ITD is found in Iraqi adult AML patients and no correlations are established between FLT3-ITD mutation and any clinical variables of AML including age, gender, total WBC count and FAB subtypes of the disease.
VL  - 1
IS  - 1
ER  -

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