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

• Main Authors: Paulus Budiono Notopuro, Paulus, Jusak Nugraha, Jusak, Budi Utomo, Budi, Harianto Notopuro, Harianto
• Format: Article PeerReviewed
• Language: English; English; Indonesian
• Published: Iranian Society of Pathology
• Subjects: R5-920 Medicine (General)
• Online Access: https://repository.unair.ac.id/120891/1/05.%20artikel.pdf; https://repository.unair.ac.id/120891/2/05.%20turnitin.pdf; https://repository.unair.ac.id/120891/3/5%20karil.pdf; https://repository.unair.ac.id/120891/; http://ijp.iranpath.org/article_43603.html; https://dx.doi.org/10.30699/ijp.2020.122579.2328
• Institution: Universitas Airlangga

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.