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

Background & Objective: Acute Promyelocytic Leukemia (APL) is a medical emergency with potentially fatal complications. APL primarily results from a chromosomal translocation (t(۱۵;۱۷)(q۲۲;q۲۱)), 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 ۱۴۵ 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 ۲۶.۰.Results: We examined ۷۵ men and ۷۰ women, with a mean age of ۳۴ years (range: ۲-۷۸ years). Besides t(۱۵;۱۷) (q۲۲;q۲۱), ۴۵.۶% had other chromosomal abnormalities. The prevalence of bcr۱ and bcr۳ isoforms was ۷۳% and ۲۷%, respectively. bcr۳ correlated with higher white blood cell (WBC) counts, additional chromosomal abnormalities, and faster Complete Hematologic Response (CHR). Early death occurred in approximately ۳۶% of all patients. The mean overall survival time was ۷۳.۵ months, with ۱۲۰-month survival rates of ۵۳.۸% for all patients and ۸۳.۹% 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, bcr۱ predominates, while bcr۳ 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-M۳ , bcr۱ , bcr۳ , PML-RARA isoforms , Iran , Survival analysis