COMPARATIVE MAPPING OF IGHG1, IGHM, FES, AND FOS IN DOMESTIC CATTLE
IMMUNOGENETICS
Authors: TOBINJANZEN, TC; WOMACK, JE
Abstract
The immunoglobulin genes have not been genetically characterized as thoroughly in cattle as in other mammals, particularly humans and mice. Comparative gene mapping in mammals suggests that the bovine immunoglobulin heavy chain genes, IGHG4 and IGHM might be syntenic with the FOS oncogene. Interestingly, however, when these genes were assigned to bovine syntenic groups utilizing a panel of bovine: hamster hybrid somatic cells, IGH genes were shown to be syntenic with the FES oncogene rather than FOS. In this study IGH and FES were assigned to Bos taurus chromsome 21 while FOS was assigned to chromosome 10. In addition, bovine-specific immunoglobulin-like sequences were observed in the hybrid somatic cells, and one, IGHML1, was mapped to bovine syntenic group U16. The probes used for somatic-cell mapping were also used to screen a small number of cattle of several different breeds for restriction fragment length polymorphisms. IGHG4 and IGHM were shown to be highly polymorphic, while FOS and FES were not.
The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia
PLOS ONE
Authors: Chen, Dongfeng; Zheng, Junxiong; Gerasimcik, Natalija; Lagerstedt, Kristina; Sjogren, Helene; Abrahamsson, Jonas; Fogelstrand, Linda; Martensson, Inga-Lill
Abstract
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.