The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia

• Published in: PloS one Vol. 11; no. 9; p. e0162638
• Main Authors: Chen, Dongfeng, Zheng, Junxiong, Gerasimcik, Natalija, Lagerstedt, Kristina, Sjögren, Helene, Abrahamsson, Jonas, Fogelstrand, Linda, Mårtensson, Inga-Lill
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.09.2016; Public Library of Science (PLoS)
• Subjects: Aberration; Acute lymphoblastic leukemia; Acute lymphocytic leukemia; B cells; B-cell receptor; Biology and Life Sciences; Bone marrow; Cancer and Oncology; Cancer och onkologi; Cell cycle; Child; Chromosomes; Copy number; Core Binding Factor Alpha 2 Subunit - metabolism; Data processing; Deoxyribonucleic acid; DNA; DNA Copy Number Variations - genetics; DNA methylation; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Genomes; Heavy Chain Disease - genetics; Heavy Chain Disease - metabolism; Hematologi; Hematology; Hospitals; Humans; Immunoglobulin Light Chains, Surrogate - genetics; Immunoglobulin Light Chains, Surrogate - metabolism; Immunoglobulin mu-Chains - genetics; Immunoglobulin mu-Chains - metabolism; Inflammation; Kinases; Leukemia; Lymphatic leukemia; Lymphocytes B; Medical prognosis; Medicine; Medicine and Health Sciences; Neoplasm Staging; Oncogene Proteins, Fusion - metabolism; Patient outcomes; Patients; Pediatrics; Pediatrik; Pre-B Cell Receptors - genetics; Pre-B Cell Receptors - metabolism; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Research and Analysis Methods; Rheumatology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Runx1 protein; Signaling; Studies; Transcription factors; Treatment Outcome
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0162638

Precursor-B cell receptor (pre-BCR) signaling represents a crucial checkpoint at the pre-B cell stage. Aberrant pre-BCR signaling is considered as a key factor for B-cell precursor acute lymphoblastic leukemia (BCP-ALL) development. BCP-ALL are believed to be arrested at the pre-BCR checkpoint independent of pre-BCR expression. However, the cellular stage at which BCP-ALL are arrested and whether this relates to expression of the pre-BCR components (IGHM, IGLL1 and VPREB1) is still unclear. Here, we show differential protein expression and copy number variation (CNV) patterns of the pre-BCR components in pediatric BCP-ALL. Moreover, analyzing six BCP-ALL data sets (n = 733), we demonstrate that TCF3-PBX1 ALL express high levels of IGHM, IGLL1 and VPREB1, and are arrested at the pre-B stage. By contrast, ETV6-RUNX1 ALL express low levels of IGHM or VPREB1, and are arrested at the pro-B stage. Irrespective of subtype, ALL with high levels of IGHM, IGLL1 and VPREB1 are arrested at the pre-B stage and correlate with good prognosis in high-risk pediatric BCP-ALL (n = 207). Our findings suggest that BCP-ALL are arrested at different cellular stages, which relates to the expression pattern of the pre-BCR components that could serve as prognostic markers for high-risk pediatric BCP-ALL patients.