The present invention relates to methods for identifying, assessing, preventing, and treating cancer (e.g., lymphoid and/or myeloid malignancies such as B-ALL in humans). A variety of histone H3K27rne3 biomarkers are provided, wherein alterations in the copy number of one or more of the biomarkers and/or alterations in the amount, structure, and/or activity of one or more of the biomarkers is associated with cancer status and indicates amenability to treatment or prevention by modulating H3K27me3 levels. The present invention further relates to methods of increasing the number of lymphoid progenitor cells (e.g., increase self-renewal and cell proliferation) by contacting the lymphoid progenitor cells (e.g., wild type and/or genomically altered cells) with an agent that inhibits polycomb repressor complex 2 (PRC2) activity or reduces H3K27roe3 levels.
