Schematic illustration of lncRNA involved in CTCF/cohesin-mediated chromatin interaction and genome topology. (A) CTCF and cohesin are frequently localized at enhancers and promoters in the genome. lncRNAs may tether and stabilize CTCF/cohesin-mediated enhancer/promoter communication by forming chromosomal loops, which lead to activation of genes required for HSC self-renewal or lineage commitment and differentiation. (B) lncRNA may coordinate with CTCF/cohesin complexes to form TAD domains in hematopoietic/AML genome. In both cases, chromatin organization results in systematic changes in gene regulatory networks and transcription programs that contribute to the promotion of hematopoietic lineage differentiation or blockage of lineage differentiation and leukemogenesis.