Although cancer classification has improved over the past 30 years, there has been no general approach for identifying new cancer classes (class discovery) or for assigning tumors to known classes (class prediction). Here, a generic approach to cancer classification based on gene expression monitoring by DNA microarrays is described and applied to human acute leukemias as a test case. A class discovery procedure automatically discovered the distinction between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) without previous knowledge of these classes. An automatically derived class predictor was able to determine the class of new leukemia cases. The results demonstrate the feasibility of cancer classification based solely on gene expression monitoring and suggest a general strategy for discovering and predicting cancer classes for other types of cancer, independent of previous biological knowledge. The challenge of cancer treatment has been to target specific therapies to pathogenetically distinct tumor types, to maximize efficacy

Previous studies have shown that immune serums made with mouse lymphoma cells as antigens can act powerfully and to some extent specifically in ~ivo on the ce]ls of several mouse lymphomas, though none has proved powerful enough to overcome advanced lymphomatosis in susceptible mice (1). In the initial tests of the work now to be reported, conjugates were made by coupling diazotized arsanilic acid (4-arsonophenyldiazotate) with an anti-Lymphoma 6C3HED-immune rabbit serum, on the assumption that the attached arsenic might enhance the effects of the immune globulins on lymphoma cells of this type in vivo. In several experiments, arsenic-azo-immune globulin preparations indeed acted much more powerfully upon Lymphoma 6C3HED cells in vivo than did the immune globulins alone, bringing about the complete regression of established 6C3HED lymphomas in susceptible ZBC mice without harming the latter perceptibly, while untreated control animals regularly died with lymphomatosis. But further experiments promptly disclosed that arsenic-azo preparations made with a variety of other proteins (e.g.,