Highlights from this issue

A strategic question in battling B-cell acute lymphoblastic leukemia (B-ALL) is the cellular origin and subsequent evolutionary path of the disease. Chromosomal abnormalities in haematopoietic cells are the likely starting point. However, the cells which are capable of supporting disease progression vary in different B-ALLs and appear to be responsible for spreading, recurrence, and resistance to therapy. Since, B-ALL is often diagnosed at later stages, the typing of cancer cells as malignant counterparts to normal B-cell precursors is likely to be misleading. This is because the path of arrest in B-cell development in cancer may be due to a variety of factors related to oncogenic activation and tumor growth. B-cell plasticity and the ability to reacquire stem/early progenitor features further complicate the picture. On pages 600–609 of this issue, Cobaleda and Sánchez-Garciá discuss this dilemma, and its significance for the proposed cancer stem cell (CSC) hypothesis, which proposes the heterogeneous tissue organization of cancer, with cells capable of renewing the cellular diversity of the original tumor. It is argued that a given CSC phenotype should not be assumed to correlate with the cellular origin of the leukemia. The use of new mouse models of cancer which incorporate CSC theory, oncogenic reprogramming, and B-cell plasticity, may provide significant advantages in clarifying disease evolution and therefore successful therapeutic intervention. PhotoDisk, Inc.