Leukaemias of a single histological type — acute lymphoblastic leukaemia (ALL), for instance — are a mixed bag when we consider their chromosomal translocations. But do all translocations have an effect on tumour behaviour, or are some an irrelevant consequence of chromosomal instability? Leukaemias with translocations that involve the mixed-lineage leukaemia gene ( MLL ) — a transcription factor that is involved in haematopoietic cell development — are classified as ALL on the basis of histology, but Scott Armstrong and co-workers now present a strong case for redefining them as a new type of leukaemia.

The authors used oligonucleotide microarrays to compare gene-expression patterns in samples from 20 patients with conventional ALL versus 17 patients with the MLL translocation. The two sets had distinct gene-expression patterns: the MLL set underexpressed many genes involved in B-cell development, and overexpressed some genes from progenitor cells and myeloid cells. Might they be more closely related to acute myeloid leukaemia (AML) than to ALL? When the expression levels of 500 genes that best differentiate AML from ALL were used to classify the MLL samples, their expression pattern was distinct from those of both AML and ALL. This allowed the authors to define a predictor set of 100 genes that correctly classified 10 out of 10 new clinical samples.

By showing that a translocation can specify a gene-expression programme, Armstrong and colleagues have uncovered a new type of leukaemia that paves the way for the molecular classification of acute leukaemia. Patients with MLL translocations respond poorly to standard therapy for ALL, but we now have a clear rationale for the development of new therapies aimed at treating acute leukaemias on the basis of their translocations, a strategy that has already proved successful for chronic myelogenous leukaemia.