Acute Myeloid Leukemia with deletion 12p: An adverse-risk disease Free

Introduction: AML is risk categorized based on the presence and cooperation of certain cytogenetics and molecular characteristics. The deletion of 12p in AML is an infrequently discussed topic, especially in adult patients. The segment of 12p includes ETV6 gene, a transcriptional repressor in normal hematopoiesis. While previous research has demonstrated a poor prognosis in pediatric patients, there is surprisingly limited evidence about adults. This initiative aims to elucidate characteristics and outcomes in patients with newly diagnosed AML with de novo 12p deletion AML.

Methods: This retrospective cohort study was conducted at MD Anderson Cancer Center we reviewed the medical record of all patients older than 18 years newly diagnosed with AML between 2014-2024. A total of 2485 newly diagnosed AML patients were identified during this period. Inclusion criteria for the analysis were: age greater than 18 years old at diagnosis, newly diagnosed de novo (defined as greater than or equal 20% blasts) or treatment related AML (defined as AML following cytotoxic/radiation therapy for non-myeloid malignancy), confirmed 12p deletion at diagnosis and availability of NGS data. Exclusion criteria included prior history of myelodysplastic syndrome, myeloproliferative neoplasm, and relapsed or refractory AML patients. Thirty-seven newly diagnosed patients with 12p deletion who met these criteria were identified. Among the thirty-seven patients, 20 had complete NGS data available at diagnosis and were included in the final analysis.

We examined patient ages, gender distribution, white blood cell counts, (WBC) blast percentage, co-occurring cytogenetics, and mutations by NGS at diagnosis.

Results: The cohort consisted of 20 with a median age of 71 years (45-79), 80% were >60 years of age. Patients were male (65%). The median WBC, HGB, platelet and bone marrow blast counts were 3.2 x 10³K/ul, 8.6 g/dl, 40.0 K/ul and 35%, respectively, 65% were treatment related AML. Furthermore, 95% of patients exhibited complex cytogenetics including abnormalities for chromosome 5, chromosome 7 and chromosome 17 in 70% (N=14), 60% (N=12), and 55% (N=11) of the patients, respectively. In terms of common mutations in order of frequency these included TET2 in 30%, RUNX1 in 20%, SRSF2 in 20%, DNMT3A in 15%, EZH2 in 15%, and TP53 detected in a notable 70%(N=14) of the cohort (including monoallelic in 15% (N=2), and biallelic in 85% (N=12) of the cohort). Eighty percent (n=16) of the patients were treated with low intensity regimens with median OS of 10.91 months [ including 12 months with LIT+VEN (n=11), and 10 months with LIT alone (n=5)]. Among the 20% (n=4) treated with IC the median OS was only 8.7 months. Three patients went on to alloSCT (including one after IC, and two after LIT based Rx's), with a median time to alloSCT of 4.5 months, and median OS among patients who went to alloSCT (n=3) of only 11 months.

Conclusions: This analysis provides insights into the clinical characteristics, cytogenetics and molecular features of adults AML with 12p deletion and suggests that 12p aberrations are more common in older (>60 year) patients, frequently associated with therapy-related AML, adverse cytogenetics, and/or TP53m, all likely contributing to the overall poor outcomes in such patients. These findings demonstrate the necessity for further larger investigation into the implications of 12p deletion on both prognosis and optimal frontline treatments to improve outcomes.