The present disclosure describes methods of treating lymphoma that expresses a short histone H2A variant. In some embodiments, the method can comprise collecting a sample from a subject having or suspected of having lymphoma, detecting a short histone H2A variant (sH2A) expression level in the sample collected from the subject, and administering to the subject a therapeutically effective dose of an anthracycline agent, if the subject has sH2A variant expression level that is detectable. In other embodiments, the sH2A is the H2A.B variant. In other embodiments, the anthracycline agent can be aclarubicin.