Figure 7 from Cell State Transitions Drive the Evolution of Disease Progression in B-Lymphoblastic Leukemia

Patient-specific CTMC modeling gives insights about responses to possible intervention. A, Remission patients display consistently positive differentiation bias (q31 − q13 > 0), whereas relapse patients show higher variance and frequent negative values, indicating dedifferentiation. B, Schematic of cell state transitions and the proposed classes of intervention. A differentiation-promoting therapy increases transitions from CD34+/CD38− cells to the other states (green arrows), whereas a dedifferentiation-inhibiting therapy reduces transitions toward the CD34+/CD38− state (red arrows). C, For each relapse patient, long-term CTMC states (CD34−/CD38+ and CD34+/CD38−) move closer to the remission medians (magenta star, dashed lines) after promoting differentiation or blocking dedifferentiation. D, At steady state, relapse patients show increased CD34−/CD38+ fractions and higher variance compared with remission; simulated interventions partially restore this balance, with dedifferentiation inhibition showing the stronger effect. On the bottom row, time-course simulations of the CTMC model illustrate that (E) remission patients converge to a differentiated cell composition with low stem cell–like fraction, (F) relapse patients maintain higher stem cell–like fractions, and (G and H) promoting differentiation and inhibiting dedifferentiation redirect relapse dynamics toward remission-like outcomes. Importantly, inhibiting dedifferentiation transitions is a more effective approach to reducing the stem cell–like compartment.