The Expression of P53, MDM2, c-myc, and P14 ARF Genes in Newly Diagnosed Acute Lymphoblastic Leukemia Patients

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ORIGINAL ARTICLE

The Expression of P53, MDM2, c-myc, and P14ARF Genes in Newly Diagnosed Acute Lymphoblastic Leukemia Patients Mehdi Allahbakhshian Farsani1 • Mohammad Rafiee1 • Hamideh Aghaee Nezhad1 Sina Salari2 • Arshia Gharehbaghian3 • Mohammad Hossein Mohammadi1,4



Received: 15 May 2019 / Accepted: 5 October 2019 Ó Indian Society of Hematology and Blood Transfusion 2019

Abstract The treatment response of acute lymphoblastic leukemia (ALL) depends on the percentage of lymphoblasts, cytogenetic aberrations, and altered gene expression. The analysis of the gene expression is applicable for determination of risk stratification and prognosis of cancers. c-MYC, P14ARF, MDM2, and P53 play a vital role in cell survival through a functional network. This study aimed to investigate the expression of these genes, also their correlation with immunophenotypic subtypes of

Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12288-019-01214-6) contains supplementary material, which is available to authorized users. & Mohammad Hossein Mohammadi [email protected] Mehdi Allahbakhshian Farsani [email protected] Mohammad Rafiee [email protected] Hamideh Aghaee Nezhad [email protected] Sina Salari [email protected] Arshia Gharehbaghian [email protected] 1

Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2

Hematology and Bone Marrow Transplantation, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3

School of Biology, University of Tehran, Tehran, Iran

4

Department of Hematology and Blood Banking, Shahid Beheshti Paramedical School, Darband St, Tehran, Iran

ALL and the percentage of blasts. Real-time PCR was performed for the expression analysis of P53, MDM2, c-MYC, and P14ARF in the bone marrow or peripheral blood samples of 52 ALL patients and 13 normal samples as controls. The morphological analysis and flow cytometry were carried out to examine the phenotypes and percentage of lymphoblasts. The decreased expression levels of P53 and MDM2 were seen in ALL patients compared with control group. In T cell subgroup of ALL the expression of P14ARF gene was more decreased among other subgroups. The expression of MDM2 was decreased in ALL patients who were under the age of 16. Based on our study, the interaction between P53 and MDM2 might be more complex and different from reports published in previous studies. Our findings showed that MDM2 is not negatively correlated with P53, at least in our samples. It can be very effective on the current and future studies to use different techniques for analysis of genome, transcriptome, and proteome in definitive risk stratification and prognosis determination. Keywords P53  MDM2  c-MYC  P14ARF  Gene expression  Acute lymphoblastic leukemia

Introduction Acute lymphoblastic leukemia (ALL) is the most frequent leukemia in children [1] and accounts for a quarter of pediatric and adult malignan