Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1016/j.ccell.2015.02.003

Type

Journal article

Journal

Cancer Cell

Publication Date

09/03/2015

Volume

27

Pages

409 - 425

Keywords

Basic Helix-Loop-Helix Transcription Factors, Clinical Trials as Topic, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Humans, Intracellular Signaling Peptides and Proteins, Molecular Sequence Data, Phosphatidylinositol 3-Kinase, Pre-B-Cell Leukemia Transcription Factor 1, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cells, B-Lymphoid, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-6, Signal Transduction, Syk Kinase, Up-Regulation, src-Family Kinases