Rationale for targeting the pre-B-cell receptor signaling pathway in acute lymphoblastic leukemia.

Abstract

Inhibitors of B-cell receptor (BCR) and pre-BCR signaling were successfully introduced into patient care for various subtypes of mature B-cell lymphoma (e.g., ibrutinib, idelalisib). Acute lymphoblastic leukemia (ALL) typically originates from pre-B cells that critically depend on survival signals emanating from a functional pre-BCR. However, whether patients with ALL benefit from treatment with (pre-) BCR inhibitors has not been explored. Recent data suggest that the pre-BCR functions as tumor suppressor in the majority of cases of human ALL. However, a distinct subset of human ALL is selectively sensitive to pre-BCR antagonists.

• Authors: Markus Müschen
• Journal: Blood (Blood) Vol. 125 Issue 24 Pg. 3688-93 (Jun 11 2015) ISSN: 1528-0020 [Electronic] United States
• PMID: 25878119 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2015 by The American Society of Hematology.

Chemical References

• BCL6 protein, human
• DNA-Binding Proteins
• Piperidines
• Pre-B Cell Receptors
• Proto-Oncogene Proteins c-bcl-6
• Purines
• Pyrazoles
• Pyrimidines
• Quinazolinones
• Receptors, Antigen, B-Cell
• STAT5 Transcription Factor
• ibrutinib
• Adenine
• idelalisib

Topics

• Adenine (analogs & derivatives)
• DNA-Binding Proteins (analysis, metabolism)
• Humans
• Molecular Targeted Therapy
• Piperidines
• Pre-B Cell Receptors (antagonists & inhibitors, metabolism)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, metabolism, pathology)
• Precursor Cells, B-Lymphoid (drug effects, metabolism, pathology)
• Proto-Oncogene Proteins c-bcl-6
• Purines (pharmacology, therapeutic use)
• Pyrazoles (pharmacology, therapeutic use)
• Pyrimidines (pharmacology, therapeutic use)
• Quinazolinones (pharmacology, therapeutic use)
• Receptors, Antigen, B-Cell (antagonists & inhibitors, metabolism)
• STAT5 Transcription Factor (metabolism)
• Signal Transduction (drug effects)