AF1q Is a Novel Poor Prognostic Marker for Adult Acute Myelogenous Leukemia (AML) Patients with Normal Cytogenetics.

Adult AML with normal cytogenetics accounts for 45–55% of de novo AML patients, who usually are categorized as intermediate-risk but have wide 5-yr overall survival (OS) rates between 24–42%. The optimal post-remission treatment strategies, especially hematopoietic stem cell transplantation (HSCT), are yet to be defined. Recent molecular studies suggested that clinical outcome may be predicted by presence or absence of mutation or changes in expression of specific genes such as FMS-like tyrosine 3 (FLT3). The AF1q gene, an MLL fusion partner, originally was identified in an AML patient’s leukemic cells with t(1; 11) (q21; q23) abnormalities. We previously found that high AF1q expression is an independent poor-prognosticator for OS and disease-free survival (DFS) in pediatric AML patients. Data indicated that allogeneic HSCT in AML patients with high AF1q expression might improve survival. To test this hypothesis in adults, we studied leukemia marrow AF1q expression by real-time polymerase chain reaction (Q-PCR) in 290 normal cytogenetic adult AML patients treated within a trial of the German AML Study Initiative Leukemia (DSIL). Patients were induced with two cytarabine-based cycles followed by consolidation therapy. Forty-eight patients received allogeneic and 58 patients received autologous HSCT after initial induction. Over 95% of AML patients had elevated AF1q expression compared to control with highest up to 409-fold. Quartile analysis of the study population showed that the highest AF1q expression trended toward worse OS (p=0.09) and DFS (p=0.1) compared to low AF1q expression despite similar complete remission rates after induction (low 66% vs. high 69%). High AF1q expression was significantly associated with the presence of an FLT3 ITD mutation (p=0.013). Patients with high AF1q expression given allogeneic HSCT had a similar OS and DFS compared to pts with low AF1q expression (62% & 56% vs 64% & 62% at 3 yr, respectively). In fact, autologous HSCT showed an inferior OS (median 25 mo vs. median not reached, p=0.04) and DFS (p=0.09) in the high AF1q group compared to the low expression group. These data suggest that high AF1q expression may be a useful molecular prognostic marker for poor prognosis adult AML patients with normal cytogenetics and allogeneic HSCT may improve OS. Further studies are focusing on whether AF1q is interactive with FLT3 in leukemogenesis as well as serving as a simultaneous therapeutic target for AML with FLT3 mutation.