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

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.