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Abstract: The PU.1 transcription factor is a crucial regulator of hematopoiesis which expression is altered in various leukemic processes. Our previous work in chronic myeloid leukemia (CML) cells demonstrated that interferon-α upregulated PU.1 expression. Here we show that expression of PU.1 is severely impaired in patients with CML at diagnosis. However, the PU.1 suppression is abrogated in patients in remission, after interferon-α or imatinib treatment. These effects are not found in patients with other myeloproliferative diseases such as polycythemia vera or essential thrombocythemia. PU.1 could, therefore, be used as an additional marker of the response to the treatment of the CML. [Copyright &y& Elsevier]

Abstract: Introduction: We conducted a follow-up study to evaluate the outcome of a heroin-dependent population 25years after their first enrollment in methadone maintenance treatment (MMT). We assessed mortality in the sample plus actual drug use, treatment, and medical factors associated with drug dependence, focusing on possible gender differences. Methods: Prospective follow-up study of 214 heroin-dependent patients consecutively admitted for MMT between 1980 and 1984 in the Asturias Public Health Service. The standardized mortality ratio (SMR) and 95% confidence interval (CI) were calculated. An ad-hoc protocol on drug misuse and treatment, drug-related morbidity and Clinical Global Impression (CGI) scores were assessed in the survivors'' sample. Results: Information was received on 159 subjects, 106 of whom were deceased. Men accounted for 76.2% of the study cohort. Over the 25-year follow-up period, the SMR was 22.51 (95% CI=22.37–22.64). In the survivors sample, 39.6% were still enrolled in MMT; human immunodeficiency virus (HIV) was diagnosed in 47.2% and hepatitis B/C in 81.1%; current heroin use was reported by 22.6%. There were no gender differences in mortality or HIV and hepatitis B/C status. None of the female survivors were using heroin at the 25-year follow-up compared with 31.1% of males. Conclusions: This study confirms the high mortality of heroin addicts even after enrollment in MMT. Severity of the addiction in terms of mortality was similar in both genders. Women who survived the 25-year follow-up were more likely to have stopped using heroin than men. [Copyright &y& Elsevier]

SKP2 is the ubiquitin ligase subunit that targets p27KIP1 (p27) for degradation. SKP2 is induced in the G1-S transit of the cell cycle, is frequently overexpressed in human cancer, and displays transformation activity in experimental models. Here we show that MYC induces SKP2 expression at the mRNA and protein levels in human myeloid leukemia K562 cells with conditional MYC expression. Importantly, in these systems, induction of MYC did not activate cell proliferation, ruling out SKP2 up-regulation as a consequence of cell cycle entry. MYC-dependent SKP2 expression was also detected in other cell types such as lymphoid, fibroblastic, and epithelial cell lines. MYC induced SKP2 mRNA expression in the absence of protein synthesis and activated the SKP2 promoter in luciferase reporter assays. With chromatin immunoprecipitation assays, MYC was detected bound to a region of human SKP2 gene promoter that includes E-boxes. The K562 cell line derives from human chronic myeloid leukemia. In a cohort of chronic myeloid leukemia bone marrow samples, we found a correlation between MYC and SKP2 mRNA levels. Analysis of cancer expression databases also indicated a correlation between MYC and SKP2 expression in lymphoma. Finally, MYC-induced SKP2 expression resulted in a decrease in p27 protein in K562 cells. Moreover, silencing of SKP2 abrogated the MYC-mediated down-regulation of p27. Our data show that SKP2 is a direct MYC target gene and that MYC-mediated SKP2 induction leads to reduced p27 levels. The results suggest the induction of SKP2 oncogene as a new mechanism for MYC-dependent transformation. [ABSTRACT FROM AUTHOR]

Abstract: Imatinib is a Bcr-Abl inhibitor used as first-line therapy of chronic myeloid leukemia (CML). p21Cip1, initially described as a cell cycle inhibitor, also protects from apoptosis in some models. We describe that imatinib down-regulates p21Cip1 expression in CML cells. Using K562 cells with inducible p21 expression and transient transfections we found that p21 confers partial resistance to imatinib-induced apoptosis. This protection is not related to the G2-arrest provoked by p21, a decrease in the imatinib activity against Bcr-Abl or a cytoplasmic localization of p21. The results suggest an involvement of p21Cip1 in the response to imatinib in CML. [Copyright &y& Elsevier]

• COVID-19 lockdown left parents as the sole respondents for their children's needs. • We examine parents' reports on the response their child received to their needs during the lockdown. • Parents of older children reported less fulfillment of children's needs. • Societies must ensure pandemics do not create context for child neglect. The ecosystemic approach to children's needs demands a cohesive response from societies, communities, and families. During the COVID-19 pandemic, the choices societies made to protect their community members from the virus could have created contexts of child neglect. With the closure of services and institutions, societies were no longer available to help meet the needs of children. The purpose of this study is to examine parents' reports on the response their children received to their needs during the COVID-19 crisis. During the period of the spring 2020 lockdown, 414 parents in the province of Quebec, Canada, completed an online questionnaire about the impact of the crisis on the response their children received to their needs. Compared to parents of younger children, parents of older children reported less fulfillment of their child's needs in three measured domains, namely cognitive and affective, security, and basic care needs. These results are discussed in light of the policies and the resources societies have put in place during the crisis to help families meet the needs of their children. Societies must learn from this crisis to put children at the top of their priorities in the face of a societal crisis. Thoughtful discussions and energy must be given to ensure that, while facing a crisis, the developmental trajectories of children are not sacrificed. [ABSTRACT FROM AUTHOR]