Prognostic Significance of the Number of Copy Numbervariations by Mlpa Technique in Acute Lymphoblastic Leukemia

Abstract

Introduction: Acute lymphoblastic leukemia (ALL) is a hematological malignancy with a higher frequency in children than in adults. Adult ALL is associates with increased morbidity and mortality and a significantly lower survival rate compared to its pediatric counterpart with an average survival of 40% at 5 years. The prognosis of patients with ALL is determined by multiple factors, such as age, tumor syndrome, white blood cell counts, cytogenetic abnormalities, and therapeutic response. The Multiplex Ligation dependent Probe Amplification technique (MLPA) is used to determine the copy number variations (CNV) of several key genes involved in disease progression and resistance, such as IKAROS family zinc finger 1 (IKZF1), PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A/2B, CRLF2. In this study, we sought to investigate the relationship between these genetic markers and standard prognostic factors in a small cohort of adult ALL patients with the aim of improving our risk stratification strategies. Materials and Methods: We investigated a group of 29 patients diagnosed with B- ALL at the Hematology Clinic of the Iasi Regional Oncology Institute between 2017 and 2021. DNA extraction and MLPA analysis were performed according to the standard technical protocol. Results: MLPA analysis reported deletions in 61% of cases and duplications in 39% of the investigated cases. The most frequent deletion identified was IKZF1 (31 %), followed by CDKN2A/2B (24.1 %), PAX5 (17.2 %), RB1 (17.2 %), ETV6 (10.3%) and, lastly, JAK2 (6.9 %). Conclusions: Our study demonstrated similar CNV profiles as in the literature data, which proves that these mutations could potentially play a role in a more sensitive risk stratification score.