Sister chromatid cohesion defects are associated with chromosomal copy number heterogeneity in high hyperdiploid childhood acute lymphoblastic leukemia.

摘要: High hyperdiploid acute lymphoblastic leukemia (ALL) is one of the most common malignancies in children. The main driver event this disease a nonrandom aneuploidy consisting gains whole chromosomes but without overt evidence chromosomal instability (CIN). Here, we investigated frequency and severity defective sister chromatid cohesion—a phenomenon related to CIN—in primary pediatric ALL. We found that large proportion (86%) cases displayed aberrant cohesion, frequently severe, compare with 49% ETV6/RUNX1-positive ALL, which mostly mild defects. In cohesion defects were associated increased copy number heterogeneity, could indicate CIN. Furthermore, correlated RAD21 NCAPG mRNA expression, suggesting link reduced cohesin condensin levels Knockdown an ALL cell line led defects, mitoses, heterogeneity numbers, similar what was seen summary, our study shows frequent heterogeneous high ranging from very severe possibly due low or levels. Cases chromosome indicative These abnormalities may play role clonal evolution