The prognostic value of Bcl-XL gene expression for remission induction is influenced by cytogenetics in adult acute myeloid leukemia

Background and Objectives. There is growing evidence that altered expressio n of genes belonging to the BcL-2 family of apoptosis regulators might infl uence chemotherapy-induced apoptosis in malignant cells and therefore could confer multidrug resistance. So far expression studies of apoptosis-regula ting genes on acute myeloid leukemia (AML) have mainly focused on Bcl-2 its elf and most of them have not included other factors involved in drug resis tance or apoptosis as parameters determining response to chemotherapy, dise ase progression and survival. Design and Methods. We therefore examined Bcl-2, Bcl-XL and Bar gene expres sion in 235 adult patients with de novo or secondary myeloid leukemia. The expression levels were correlated with established prognostic factors such as age, cytogenetic aberrations, mdr1 gene expression and clinical outcome In a multivariate analysis. Results. Bcl-2 and Bcl-XL positive patient had a much lower white blood cel l counts than negative patient (p <0.001 and p=0.003, respectively). Bcl-2 expression correlated with FAB subtype MO (p=0.03), Bar with M5b (p=0.02) a nd Bcl-XL with M6 (p=0.005). Mdr1 expression was more frequently seen in Bc l-2 and Bcl-XL positive patients (p-0.03 and p=0.02, respectively). Remarka bly Bar was significantly less frequently expressed in de novo AML patients with high risk cytogenetics (p=0.007). No difference in expression was rec ognized for Bcl-2 or Bcl-XL when statistical analyses were done for cytogen etic risk groups. However, in the multivariate analysis regarding the group of de novo AML patients I 60 years with intermediate risk cytogenetics, Bc l-XL expression was found to be an independent negative prognostic factor f or response to induction therapy (p=0.04). In contrast, no prognostic impac t of Bcl-XL expression on treatment response was seen within the group of p atients with high risk cytogenetic findings. Neither Bcl-2 nor Bar nor Bcl- XL expression had a significant influence on overall or disease-free surviv al. Interpretation and Conclusions. These data indicate that the prognostic val ue of Bcl-XL gene expression for treatment response in AML patients less th an or equal to 60 years is dependent on cytogenetics. (C) 2001, Ferrata Sto rti Foundation.