The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia.
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.
Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Dongfeng
D
Chen
Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Junxiong
J
Zheng
Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Natalija
N
Gerasimcik
Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Kristina
K
Lagerstedt
Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
Helene
H
Sjögren
Queen Silvia Children's Hospital, Gothenburg, Sweden.
Jonas
J
Abrahamsson
Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.|Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Linda
L
Fogelstrand
Department of Rheumatology and Inflammation Research, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Inga-Lill
IL
Mårtensson
D002648:Child; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D056915:DNA Copy Number Variations / Q000235:genetics; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006362:Heavy Chain Disease / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D054444:Immunoglobulin Light Chains, Surrogate / Q000235:genetics* / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D054420:Pre-B Cell Receptors / Q000235:genetics* / Q000378:metabolism; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D000097764:ETS Translocation Variant 6 Protein
D050676:Core Binding Factor Alpha 2 Subunit; D054444:Immunoglobulin Light Chains, Surrogate; D007148:Immunoglobulin mu-Chains; D015514:Oncogene Proteins, Fusion; D054420:Pre-B Cell Receptors; D012333:RNA, Messenger; C041229:IGHM protein, human; C515635:IGLL1 protein, human; C543638:TCF3-PBX1 fusion protein, human; C102421:TEL-AML1 fusion protein; D000097764:ETS Translocation Variant 6 Protein; C515639:VPREB1 protein, human