Figure 1.

Dynamics of normal and chronic myeloid leukemia (CML) cells in hematopoiesis. Normal (blue) and leukemic (red) stem cells may coexist under neutral drift at the level of the stem cell pool. Downstream of the stem cell pool, cells that are selected to replicate differentiate with probability ε or self-renew with probability 1 − ε (top inset). Differentiation leads to migration of cells to the next downstream compartment (on the right, see time arrow) while self-renewal keeps the daughter cells in the same compartment as their parent. Progenitor cells produced from stem cell replication populate downstream hematopoietic compartments. BCR-ABL expression increases the relative fitness of CML cells (different shades of red and yellow), enabling them to gradually take over hematopoiesis (normal progenitors depicted in different shades of blue). As a result, the clone expands and is increasingly represented in downstream hematopoietic compartments. BCR-ABL expression has no impact on mature cells. The impact of BCR-ABL on the more mature cells is unclear at present. Imatinib therapy affects a fraction of CML cells (in different shades of green) and reduces their relative fitness compared to normal cells. Imatinib has no impact on stem cells or mature cells.