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. 2020 Apr 20;1(1):32–47. doi: 10.1158/2643-3230.BCD-19-0028

Figure 7.

Figure 7. Model illustrating how multiple, converging pathways may lead to t-MN. Left, various predisposing factors that may influence whether a patient develops t-MN. A patient may have no predisposing factors, have an inherited mutation (predisposing them to aberrant DNA repair), have a preexisting somatic mutation (CHIP), or have an aberrant BM microenvironment (due to aging and/or chronic inflammation). Middle, how multiple cycles of cytotoxic therapy may promote clonal expansion of cells with preexisting and/or newly acquired mutations and alter the BM microenvironment, possibly via therapy-induced senescence. Together, this creates permissive conditions for malignant transformation of hematopoietic cells. Right, how these changes converge to deregulate the DNA damage response and cell-cycle checkpoint, as well as enhance metabolism and survival, ultimately leading to t-MN.

Model illustrating how multiple, converging pathways may lead to t-MN. Left, various predisposing factors that may influence whether a patient develops t-MN. A patient may have no predisposing factors, have an inherited mutation (predisposing them to aberrant DNA repair), have a preexisting somatic mutation (CHIP), or have an aberrant BM microenvironment (due to aging and/or chronic inflammation). Middle, how multiple cycles of cytotoxic therapy may promote clonal expansion of cells with preexisting and/or newly acquired mutations and alter the BM microenvironment, possibly via therapy-induced senescence. Together, this creates permissive conditions for malignant transformation of hematopoietic cells. Right, how these changes converge to deregulate the DNA damage response and cell-cycle checkpoint, as well as enhance metabolism and survival, ultimately leading to t-MN.