Brownian Bridging of Chromatin States in Leukemic Cells

Chromatin mobility in living interphase nuclei provides a dynamical readout of genome regulation. From time-resolved trajectories of chromatin granules in primary acute lymphoblastic leukemia (ALL) samples (one B-ALL, one T-ALL), leukemic cell lines (U266, Jurkat), and healthy donor T lymphocytes, we resolve rare but reproducible transitions between extreme mobility states. We quantify these events with Brownian-bridge ensembles, i.e., trajectories conditioned on crossings between low- and high-mobility quartiles. Despite their low frequency, crossings reveal strong polarity: activation ( Q1 → Q4 ) concentrates on a superlinear, ballistic-like ridge, whereas reconfinement ( Q4 → Q1 ) returns more slowly toward confinement. The scarcity of extreme events is comparable in magnitude to reported bursting fractions, motivating future joint live-imaging tests that directly link mobility bridges to transcriptional state. These asymmetric pathways yield a compact dynamical signature of disrupted confinement and lineage-dependent nuclear deregulation in ALL, and generate testable predictions for cohort-level validation.