Abstract: Described are biomarkers and associated methods for determining a prognosis for a subject with leukemia and/or for detecting Leukemic Regenerating Cells (LRCs) or Hematopoietic Regenerating Cells. While chemotherapy may successfully deplete leukemic stem cells (LSCs), a molecularly distinct population of LRCs are observed following cytotoxic chemotherapy not seen in therapy naïve subjects with leukemia or healthy hematopoietic cell populations. Also described are methods for the treatment of leukemia that target LRCs in a subject in need thereof.