title: 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: Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA.
authors: Markus
authors: M
authors: Müschen
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D010880:Piperidines; D054420:Pre-B Cell Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D054448:Precursor Cells, B-Lymphoid / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051560:Proto-Oncogene Proteins c-bcl-6; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D052999:Quinazolinones / Q000494:pharmacology / Q000627:therapeutic use*; D011947:Receptors, Antigen, B-Cell / Q000037:antagonists & inhibitors / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D010880:Piperidines; D054420:Pre-B Cell Receptors; D051560:Proto-Oncogene Proteins c-bcl-6; D011687:Purines; D011720:Pyrazoles; D011743:Pyrimidines; D052999:Quinazolinones; D011947:Receptors, Antigen, B-Cell; D050799:STAT5 Transcription Factor; C551803:ibrutinib; D000225:Adenine; C552946:idelalisib