[PDF][PDF] Self-enforcing feedback activation between BCL6 and pre-B cell receptor signaling defines a distinct subtype of acute lymphoblastic leukemia

H Geng, C Hurtz, KB Lenz, Z Chen, D Baumjohann… - Cancer cell, 2015 - cell.com
H Geng, C Hurtz, KB Lenz, Z Chen, D Baumjohann, S Thompson, NA Goloviznina, WY Chen…
Cancer cell, 2015cell.com
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 …
Summary
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.
cell.com