Intragenic amplification of PAX5: a novel subgroup in B-cell precursor acute lymphoblastic leukemia?

Intragenic PAX5 amplification defines a novel, relapse-prone subtype of B-cell precursor acute lymphoblastic leukemia with a poor outcome

Genotoxic signature in cord blood cells of newborns exposed in utero to a Zidovudine-based antiretroviral combination

International audienceBACKGROUND: The genotoxicity of zidovudine has been established in experimental models. The objective of the study was to identify genotoxicity markers in cord blood cells from newborns exposed in utero to antiretroviral (ARV) combinations containing zidovudine. METHODS: Cells were investigated by karyotyping and gene expression analysis of the CD34(+) hematopoietic stem/progenitor cell (HPC) compartment. RESULTS: Karyotyping of the cord blood cells from 15 ARV-exposed newborns and 12 controls revealed a higher proportion of aneuploid cells in the exposed group (median, 18.8% [interquartile range, 10.0%-26.7%] vs 6.6% [interquartile range, 3.1%-11.7%]; P < .001). All chromosomes were involved, with a random distribution of these alterations. Gene expression profiling of CD34(+) HPCs from 7 ARV-exposed and 6 control newborns revealed that >300 genes were significantly upregulated or downregulated by at least 1.5-fold in the exposed group (P < .05 for all comparisons). Significant alterations of genes involved in cell cycle control, mitotic checkpoints, and DNA repair were identified. Although this study does not allow discrimination between the roles of each of the 3 drugs, both cytogenetic and transcriptional findings are similar to those in cellular experiments that used zidovudine alone. CONCLUSIONS: The cord blood cells, including hematopoietic stem cells, from newborns exposed in utero to a zidovudine-based ARV combination present cytogenetic and transcriptional abnormalities compatible with DNA damage

Genotoxic signature in cord blood cells of newborns exposed in utero to a Zidovudine-based antiretroviral combination

International audienceBACKGROUND: The genotoxicity of zidovudine has been established in experimental models. The objective of the study was to identify genotoxicity markers in cord blood cells from newborns exposed in utero to antiretroviral (ARV) combinations containing zidovudine. METHODS: Cells were investigated by karyotyping and gene expression analysis of the CD34(+) hematopoietic stem/progenitor cell (HPC) compartment. RESULTS: Karyotyping of the cord blood cells from 15 ARV-exposed newborns and 12 controls revealed a higher proportion of aneuploid cells in the exposed group (median, 18.8% [interquartile range, 10.0%-26.7%] vs 6.6% [interquartile range, 3.1%-11.7%]; P < .001). All chromosomes were involved, with a random distribution of these alterations. Gene expression profiling of CD34(+) HPCs from 7 ARV-exposed and 6 control newborns revealed that >300 genes were significantly upregulated or downregulated by at least 1.5-fold in the exposed group (P < .05 for all comparisons). Significant alterations of genes involved in cell cycle control, mitotic checkpoints, and DNA repair were identified. Although this study does not allow discrimination between the roles of each of the 3 drugs, both cytogenetic and transcriptional findings are similar to those in cellular experiments that used zidovudine alone. CONCLUSIONS: The cord blood cells, including hematopoietic stem cells, from newborns exposed in utero to a zidovudine-based ARV combination present cytogenetic and transcriptional abnormalities compatible with DNA damage

Diet variability among pre‐Dogon and early Dogon populations (Mali) from stable isotopes and dental diseases

This paper reports on diet variability in the Dogon Country (Mali) through a bio-archaeological study of pre-Dogon and early Dogon human remains (7th c. to 19th c. AD) from collective burial caves in the Bandiagara Escarpment. 220 crania from collections curated in Leiden, Paris and Bamako were studied for dental diseases. In a subset of teeth (n = 175), δ13C and δ15N were measured in bulk dentine samples. δ13C and δ15N values vary widely (-15.4 to -6.0‰ for δ13C, 6.0 to 14.8‰ for δ15N, n = 175), and indicate diets dominated by C4-based foods with a focus on plants; animal products played a minor role. There are significant differences between the δ13C values from older (pre-Dogon) and younger (Dogon) periods. Frequencies of caries, AMTL and abscesses increase significantly through time. Individuals from northern caves have more positive δ13C and δ15N values than southern ones. The temporal shifts are probably due to progressive diversification of foods, consistent with archaeological evidence showing the addition of rice and vegetables to pearl millet. The geographical disparity is explained by a combination of climatic, environmental and cultural factors. Last, inter-site differences imply that different communities (or sub-sections thereof) disposed of their dead in different caves. Based on a large sample extending over a wider area and longer time frame than previous work, our study shows that diets in the Dogon Country were neither uniform nor continuous through time, as previously proposed. Our results attest to a complex history of settlement and foodways