[Molecular diagnosis and therapeutic strategy for Philadelphia chromosome-positive acute leukemia]

We focused on biological characteristics of Philadelphia chromosome-positive acute leukemia (Ph+ AL) and treated those patients with BHAC-DMPV induction chemotherapy. After obtaining complete remission, we attempted to treat with allogeneic bone marrow transplantation, while those without suitability for marrow transplantation were treated with alpha-interferon (IFN-alpha), in order to obtain prolong remission status. Chromosomal and molecular analyses, including BCR rearrangement and BCR -ABL mRNA, before and after IFN-alpha treatment demonstrated a recovery of normal hematopoiesis by the treatment of INF-alpha, however, suppressive effect for the blast cells by IFN-alpha was insufficient. To clarify the mechanism of IFN-alpha on the Ph+ leukemia cells, we studied expression of interferon stimulated genes (ISGs). However, an association between expression of ISGs and therapeutic effectiveness was not evident. Although, the exact anti-neoplastic mechanism of IFN-alpha is not established yet, our study demonstrated the possibility for utilization of IFN-alpha in some Ph+ AL patients as a maintenance therapy to obtain long survivals. Therefore, studies using a large number of patients with Ph+ AL should be performed, in order to establish induction and maintenance therapies reflecting biological characteristics of Ph+ AL.