| First Author | Geng H | Year | 2015 |
| Journal | Cancer Cell | Volume | 27 |
| Issue | 3 | Pages | 409-25 |
| PubMed ID | 25759025 | Mgi Jnum | J:219919 |
| Mgi Id | MGI:5629984 | Doi | 10.1016/j.ccell.2015.02.003 |
| Citation | Geng H, et al. (2015) Self-Enforcing Feedback Activation between BCL6 and Pre-B Cell Receptor Signaling Defines a Distinct Subtype of Acute Lymphoblastic Leukemia. Cancer Cell 27(3):409-25 |
| abstractText | Studying 830 pre-B ALL cases from four clinical trials, we found that human ALL can be divided into two fundamentally distinct subtypes based on pre-BCR function. While absent in the majority of ALL cases, tonic pre-BCR signaling was found in 112 cases (13.5%). In these cases, tonic pre-BCR signaling induced activation of BCL6, which in turn increased pre-BCR signaling output at the transcriptional level. Interestingly, inhibition of pre-BCR-related tyrosine kinases reduced constitutive BCL6 expression and selectively killed patient-derived pre-BCR(+) ALL cells. These findings identify a genetically and phenotypically distinct subset of human ALL that critically depends on tonic pre-BCR signaling. In vivo treatment studies suggested that pre-BCR tyrosine kinase inhibitors are useful for the treatment of patients with pre-BCR(+) ALL. |
