Iranian Journal of Pathology

Different Isoforms of PML-RARA Chimeric Protein in Patients with Acute Promyelocytic Leukemia: Survival Analysis per Demographic Characteristics, Clinicohematological Parameters, and Cytogenetic Findings

Document Type : Original Research

Authors

Sarah Siahbani 1
Akbar Safaie 1
Masoumeh Faghih 1
Marzieh Hosseini 1
Afsaneh Fendereski 2
Behnaz Valibeigi 1
Ahmad Monabati 1

1 Molecular Pathology and Cytogenetic Ward, Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Biostatistics, School of Health, Health Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran

https://doi.org/10.30699/ijp.2023.2007229.3145
Abstract
Background & Objective: Acute Promyelocytic Leukemia (APL) is a medical emergency with potentially fatal complications. APL primarily results from a chromosomal translocation (t(15;17)(q22;q21)), leading to the formation of the PML-RARA fusion gene with three possible isoforms. This study aims to investigate the characteristics of Iranian APL patients, the distribution of PML-RARA isoforms, and survival analysis.
Methods: We included 145 consecutive eligible patients in this study. Data were collected through archived documents and phone inquiries, following consent. Subsequently, we analyzed the data using SPSS software version 26.0.
Results: We examined 75 men and 70 women, with a mean age of 34 years (range: 2-78 years). Besides t(15;17) (q22;q21), 45.6% had other chromosomal abnormalities. The prevalence of bcr1 and bcr3 isoforms was 73% and 27%, respectively. bcr3 correlated with higher white blood cell (WBC) counts, additional chromosomal abnormalities, and faster Complete Hematologic Response (CHR). Early death occurred in approximately 36% of all patients. The mean overall survival time was 73.5 months, with 120-month survival rates of 53.8% for all patients and 83.9% for those who achieved CHR. Univariate analysis identified old age, relapse, lower platelet (PLT) counts, higher WBC counts, and leukocytosis as survival risk factors. However, in multivariate analysis, only old age and higher WBC counts were identified as adverse prognostic factors.
Conclusion: In Iranian APL patients, bcr1 predominates, while bcr3 correlates with higher WBC counts, high-risk categorization, additional chromosomal abnormalities, and faster CHR. Survival is negatively impacted by old age, relapse, lower PLT counts, higher WBC counts, and leukocytosis.

Keywords

APL
AML-M3
bcr1
bcr3
PML-RARA isoforms
Iran
Survival analysis

Subjects

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Iranian Journal of Pathology
Volume 18, Issue 4
Autumn 2023
Pages 456-475

  • Receive Date 17 July 2023
  • Revise Date 03 October 2023
  • Accept Date 03 October 2023

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