| First Author | Luo H | Year | 2019 |
| Journal | Cancer Cell | Volume | 36 |
| Issue | 6 | Pages | 645-659.e8 |
| PubMed ID | 31786140 | Mgi Jnum | J:282668 |
| Mgi Id | MGI:6381468 | Doi | 10.1016/j.ccell.2019.10.011 |
| Citation | Luo H, et al. (2019) HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-like Disease in Mice. Cancer Cell 36(6):645-659.e8 |
| abstractText | Long non-coding RNAs (lncRNAs) are critical for regulating HOX genes, aberration of which is a dominant mechanism for leukemic transformation. How HOX gene-associated lncRNAs regulate hematopoietic stem cell (HSC) function and contribute to leukemogenesis remains elusive. We found that HOTTIP is aberrantly activated in acute myeloid leukemia (AML) to alter HOXA-driven topologically associated domain (TAD) and gene expression. HOTTIP loss attenuates leukemogenesis of transplanted mice, while reactivation of HOTTIP restores leukemic TADs, transcription, and leukemogenesis in the CTCF-boundary-attenuated AML cells. Hottip aberration in mice abnormally promotes HSC self-renewal leading to AML-like disease by altering the homeotic/hematopoietic gene-associated chromatin signature and transcription program. Hottip aberration acts as an oncogenic event to perturb HSC function by reprogramming leukemic-associated chromatin and gene transcription. |
