Review Article

Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity?

Figure 2

Potential mechanisms of lineage switching in acute leukemias. The existence of bipotential progenitors, cell reprogramming, dedifferentiation, clonal selection, and seeding of donor cells are proposed to participate in leukemic cell fates conversion. Microenvironment may influence all proposed mechanisms by modulating the genome plasticity of the cells and change the leukemia outcome at relapse. Black arrows follow normal differentiation, whereas green arrows indicate potential mechanisms of lineage switching. Bipotential progenitors might be responsible for fate interconversions from mixed lymphoid-myeloid leukemias. Genetic and epigenetic changes in transcription factors of fully committed or developing cells are the basis of cellular reprogramming. During dedifferentiation, a cellular change occurs in a differentiated state which in turn get back to a more primitive and less committed stage. Clonal selection is based on the existence of an oligoclonal disease, and the selection of a distinct and chemoresistant clone. In seeding of donor cell leukemia after allografts from bone marrow, a first “hit” may take place in donor followed by a second “hit” in the recipient, along with a clonal selection upon time. B/M: bipotent B and myeloid progenitor; T/M: bipotent T and myeloid progenitor; AML: acute myeloid leukemia; B-ALL: acute lymphoblastic leukemia from B precursors; T-ALL: acute lymphoblastic leukemia from T precursors; L: lymphoid progenitors; M: myeloid progenitors; t: time.
406796.fig.002