FoxO3 Is a Biomarker for BCR-ABL Positive Leukemia.
Rajan Dewar, Sing-Tsung Chen, Heather-Yeckes Rodin, Kenneth Miller, Roya Khosravi-Far. Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA; Clarient Inc.,, Aliso Viejo, CA; Tufts University Medical Center, Boston, MA
Background: FoxO3 is a pro-apoptotic protein, which is a member of the FKHRL family with multiple nuclear targets. Recent animal studies show that FoxO3 is downregulated in BCR-ABL positive leukemia. FoxO3 has also been implicated with resistant leukemic stems in chronic myelogenous leukemia (CML). Intracellular FoxO3 can be regulated by pharmacologic agents. Thus, FoxO3 appears to be an important theranostic marker in CML and therapy resistant Ph-chromosome positive ALL (Ph+ALL).
Design: This study was performed in serially diagnosed and archived bone marrow samples of CML and Ph+ALL and matched controls. A total of 14 cases were identified. They included 4 CML; 4 Ph+ALL; 2 Ph-ALL & 4 controls. Mean age was 46.5 years (8 males/6 females). Bone marrow core biopsies were stained for FoxO3 (Millipore; 1:100) and expression of FoxO3 was analyzed within the precursor cell population (figures 1&2). Expression in >20% of neoplastic cells was taken to be positive expression.
Results: FoxO3 was significantly (p=0.031; two tailed t-test) downregulated in 5 of 8 cases of Ph+ALL and CML.
None of the 6 controls (Ph-ve ALL or benign controls) showed downregulation of FoxO3.
This is shown in the table.