Evaluation of the role of TAX, HBZ, and HTLV-1 proviral load on the survival of ATLL patients

Mohammad Mehdi Akbarin; Abbas Shirdel; Alireza Bari; Seyedeh Tahereh Mohaddes; Houshang Rafatpanah; Ehsan Ghayour Karimani; Kobra Etminani; Amin Golabpour; Reza Torshizi

doi:10.5045/br.2017.52.2.106

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Original Article

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Blood Res 2017; 52(2):

Published online June 22, 2017

https://doi.org/10.5045/br.2017.52.2.106

Evaluation of the role of TAX, HBZ, and HTLV-1 proviral load on the survival of ATLL patients

Mohammad Mehdi Akbarin¹, Abbas Shirdel², Alireza Bari², Seyedeh Tahereh Mohaddes², Houshang Rafatpanah¹, Ehsan Ghayour Karimani³, Kobra Etminani⁴, Amin Golabpour⁴, and Reza Torshizi⁵

Author Info. +

¹Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical sciences, Mashhad, Iran.

²Hematology Department, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciencess, Mashhad, Iran.

³Molecular Diagnostic Unit, Research and Education Department, Razavi Hospitals, Mashhad, Iran.

⁴Department of Medical Informatics, Molecular Medicine Department, Faculty of Medicine, Mashhad University of Medical sciences, Mashhad, Iran.

⁵Department of Modern Sciences and Technologies, Molecular Medicine Department, Faculty of Medicine, Mashhad University of Medical sciences, Mashhad, Iran.

Correspondence to : Reza Torshizi, Ph.D. Department of Modern Sciences and Technologies, Mashhad University of Medical Sciences, Mashhad, Razavi Khorasan 91388-13944, Iran. torshiziR901@mums.ac.ir

Received: December 24, 2016; Revised: February 15, 2017; Accepted: March 14, 2017

Abstract

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Abstract

Background

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with very poor prognosis and short survival, caused by the human T-lymphotropic virus type-1 (HTLV-1). The HTLV-1 biomarkers trans-activator x (TAX) and HTLV-1 basic leucine zipper factor (HBZ) are main oncogenes and life-threatening elements. This study aimed to assess the role of the TAX and HBZ genes and HTLV-1 proviral load (PVL) in the survival of patients with ATLL.

Methods

Forty-three HTLV-1-infected individuals, including 18 asymptomatic carriers (AC) and 25 ATLL patients (ATLL), were evaluated between 2011 and 2015. The mRNA expression of TAX and HBZ and the HTLV-1 PVL were measured by quantitative PCR.

Results

Significant differences in the mean expression levels of TAX and HBZ were observed between the two study groups (ATLL and AC, P=0.014 and P=0.000, respectively). In addition, the ATLL group showed a significantly higher PVL than AC (P=0.000). There was a significant negative relationship between PVL and survival among all study groups (P=0.047).

Conclusion

The HTLV-1 PVL and expression of TAX and HBZ were higher in the ATLL group than in the AC group. Moreover, a higher PVL was associated with shorter survival time among all ATLL subjects. Therefore, measurement of PVL, TAX, and HBZ may be beneficial for monitoring and predicting HTLV-1-infection outcomes, and PVL may be useful for prognosis assessment of ATLL patients. This research demonstrates the possible correlation between these virological markers and survival in ATLL patients.

Keywords HTLV-1, ATLL, TAX, HBZ, Proviral load

Article

Original Article

Blood Res 2017; 52(2): 106-111

Published online June 22, 2017 https://doi.org/10.5045/br.2017.52.2.106

Evaluation of the role of TAX, HBZ, and HTLV-1 proviral load on the survival of ATLL patients

Mohammad Mehdi Akbarin¹, Abbas Shirdel², Alireza Bari², Seyedeh Tahereh Mohaddes², Houshang Rafatpanah¹, Ehsan Ghayour Karimani³, Kobra Etminani⁴, Amin Golabpour⁴, and Reza Torshizi⁵

¹Inflammation and Inflammatory Diseases Research Center, Faculty of Medicine, Mashhad University of Medical sciences, Mashhad, Iran.

²Hematology Department, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciencess, Mashhad, Iran.

³Molecular Diagnostic Unit, Research and Education Department, Razavi Hospitals, Mashhad, Iran.

⁴Department of Medical Informatics, Molecular Medicine Department, Faculty of Medicine, Mashhad University of Medical sciences, Mashhad, Iran.

⁵Department of Modern Sciences and Technologies, Molecular Medicine Department, Faculty of Medicine, Mashhad University of Medical sciences, Mashhad, Iran.

Correspondence to:Reza Torshizi, Ph.D. Department of Modern Sciences and Technologies, Mashhad University of Medical Sciences, Mashhad, Razavi Khorasan 91388-13944, Iran. torshiziR901@mums.ac.ir

Received: December 24, 2016; Revised: February 15, 2017; Accepted: March 14, 2017

Abstract

Background

Methods

Results

Conclusion

Keywords: HTLV-1, ATLL, TAX, HBZ, Proviral load

Abstract

Fig 1.

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Figure 1.

Survival time of adult T-cell leukemia/lymphoma (ATLL) patients according to subtype.

Blood Research 2017; 52: 106-111https://doi.org/10.5045/br.2017.52.2.106

Fig 2.

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Figure 2.

Association between survival time and proviral load (PVL) in adult T-cell leukemia/lymphoma (ATLL) patients (five PVL groups were defined to examine the impact of HTLV-1 PVL on survival among patients with ATLL).

Blood Research 2017; 52: 106-111https://doi.org/10.5045/br.2017.52.2.106

Table 1 . Primers and probes for TAX, HBZ, and β2-microglobulin..

Table 2 . Clinical manifestations and survival time of adult T-cell leukemia/lymphoma (ATLL) patients..

Table 3 . TAX and HBZ expression in adult T-cell leukemia/lymphoma (ATLL) patients and asymptomatic carriers..

^a)P<0.05..

Abbreviations: SD, standard deviation; SEM, standard error of the mean..