Iranian Journal of Pathology

The Association of FLT3-ITD Gene Mutation with Bone Marrow Blast Cell Count, CD34, Cyclin D1, Bcl-xL and hENT1 Expression in Acute Myeloid Leukemia Patients

Document Type : Original Research

Authors

Paulus Budiono Notopuro 1
Jusak Nugraha 2
Budi Utomo 3
Harianto Notopuro 4

1 Faculty of Medicine, Airlangga University, Jawa, Indonesia

2 Department of Clinical Pathology, Faculty of Medicine, Airlangga University, Jawa, Indonesia

3 Department of Public Health, Faculty of Medicine, Airlangga University, Jawa, Indonesia

4 4. Department of Biochemistry and Molecular Biology, Faculty of Medicine, Airlangga University, Jawa, Indonesia

https://doi.org/10.30699/ijp.2020.122579.2328
Abstract
Background & Objective:  FLT3-ITD has been recently used as a molecular prognostic marker for risk classification in acute myeloid leukemia (AML) therapy. In this study we aimed to investigate the association of FLT3-ITD gene mutation with bone marrow blast cell count, CD34 expression as malignant cell burden, cyclin D1 and Bcl-xL expressions as indexes of cell proliferation and anti-apoptosis and human equilibrative nucleoside transporter 1 (hENT1) expression as cytarabine transporter during AML treatment.
Methods:  We investigated FLT3-ITD mutations, bone marrow blast cell count, CD34, cyclin D1, Bcl-xL and hENT1 expression in bone marrow aspirates from 22 de novo AML patients in a cross sectional study.
Results:  FLT3-ITD mutations were observed in 5 out of 22 de novo AML patients (22.7%). Patient with FLT3-ITD mutations had higher blast cell counts (79.5% vs 56.1%, p =0.004). In patients with FLT3-ITD mutations, CD34 and cyclin D1 expressions were higher (MFI 328.80 vs 25.78, p =0.003 and MFI 74.51 vs 57.15 p =0.005) than the patients without mutations. hENT1 expression in AML with FLT3-ITD mutation was lower (MFI 29.64 versus 56.32, p =0.0000) than in mutation-free AML. There was no significant difference in Bcl-xL expression between patients with and without mutations (p =0.61).
Conclusion:  A significant association was found between FLT3-ITD gene mutations in AML patients with bone marrow blast cell count, CD34, cyclin D1 and hENT1 expressions, however no association was obtained with Bcl-xL expression. These findings support the role of such mutation in pathogenesis of AMLand its contribution in rearrangement of standard therapy with cytarabine in management of AML.

Keywords

AML
Bcl-xL
Blast cell count
CD34
Cyclin D1
FLT3-ITD
hENT1

Subjects

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Iranian Journal of Pathology
Volume 15, Issue 4
Autumn 2020
Pages 306-312

  • Receive Date 04 March 2020
  • Revise Date 19 April 2020
  • Accept Date 04 April 2020

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