Leukemia originates in blood-forming cells, likely hematopoietic stem or progenitor cells, within the bone marrow and is in principle classified into acute or chronic and myeloid or lymphocytic leukemia. Acute leukemia originate in more immature blood (stem) cells and progress rapidly, whereas chronic leukemia has a much slower disease progression and originates in more differentiated progenitors. Lymphocytic leukemia arises in lymphoid stem cells or their progeny, and myeloid leukemia results from transformation of myeloid progenitor cells/myeloblasts, leading to abnormal, immature white blood cells (called blasts). Leukemia invades the bone marrow, the blood and some other tissues.
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and is further subdivided into three risk categories according to (cyto-)genetic abnormalities. For example PML-RARa (arises from t(15:17)) that forms repressive complexes with RXR, HDACs, EZH2 and DNMT can be treated with all trans retinoic acid to induce dedifferentiation and has a good prognosis when combined with chemotherapy. Additional classifications include normal karyotype but some recurrent mutations (intermediate risk) or complex cytogenic abnormalities together with genetic mutations characterize an adverse risk profile. AML is a highly heterogeneous disease and commonly mutated genes include signaling molecules (e.g. receptor tyrosin kinase FLT3, c-KIT), nuclear shuttle proteins (NPM1), myeloid transcription factors (RUNX1), and epigenetic regulators (DNMT3A, IDH1/2).
With the discovery and characterization of hematopoietic stem cells, it soon became clear that leukemia, especially chronic and acute myeloid leukemia follow a similar hierarchical organization and today, much of the knowledge on cancer stem cells are derived from studies with leukemic stem cells.