Identification of novel proto-oncogenes in murine myeloid leukemias by retroviral insertional mutagenesis : the peripheral cannabinoid receptor

Dynamic and complex processes of cell proliferation, differentiation, maturation, apoptosis, and survival maintain homeostasis in bone marrow and perTheral blood. In steady state, the turnover of blood cells is approximately I x 10' cells per day. During stress conditions, such as infections or bleeding, blood cell formation is properly adjusted by the production of terminally differentiated functional cells. Leukemia is a progressive neoplastic disease of the blood cell forming system, in which non-functional blood cells accumulate in the bone marrow, thereby interfering with normal blood cell formation. The lIlain objectives of the experimental work described in this thesis lVere the identification of !lovel prolo-oncogenes or tumor suppressor genes involved ill lIlyeloid leukelllia developlllelll by using retroviral insertionallllutagenesis and the characterization of these novel genes

Programme Aid Evaluation:

Summaries With the introduction of Structural Adjustment Programmes, the objectives of programme aid shifted from relief of foreign exchange constraints to supporting policy reforms. The appraisal criteria for providing programme aid were modified accordingly, but the evaluation criteria did not change. A review of evaluation studies of Dutch programme aid and of Aide Memoires of Joint Evaluation Missions in the framework of the Special Programme of Assistance to African countries undertaking structural adjustment suggests the need for an appropriate multi?donor forum that addresses both the economic and institutional aspects of the macro?effectiveness of programme aid

Cbfbeta reduces Cbfbeta-SMMHC-associated acute myeloid leukemia in mice

The gene encoding for core-binding factor beta (CBFbeta) is altered in acute myeloid leukemia samples with an inversion in chromosome 16, expressing the fusion protein CBFbeta-SMMHC. Previous studies have shown that this oncoprotein interferes with hematopoietic differentiation and proliferation and participates in leukemia development. In this study, we provide evidence that Cbfbeta modulates the oncogenic function of this fusion protein. We show that Cbfbeta plays an important role in proliferation of hematopoietic progenitors expressing Cbfbeta-SMMHC in vitro. In addition, Cbfbeta-SMMHC-mediated leukemia development is accelerated in the absence of Cbfbeta. These results indicate that the balance between Cbfbeta and Cbfbeta-SMMHC directly affects leukemia development, and suggest that CBF-specific therapeutic molecules should target CBFbeta-SMMHC function while maintaining CBFbeta activity

COVID-19 in people with HIV in the Netherlands

OBJECTIVES: We investigated occurrence of and risk factors for severe COVID-19 outcomes in people with HIV (PWH) in the Netherlands. DESIGN: An ongoing prospective nationwide HIV cohort study. METHODS: COVID-19 diagnoses and outcomes with other relevant medical information were prospectively collected from electronic medical records in all HIV treatment centers in the Netherlands, from the start of the COVID-19 epidemic until December 31, 2021. Risk factors for COVID-19 related hospitalization and death were investigated using multivariable logistic regression, including demographics, HIV-related factors, and comorbidities. RESULTS: The cohort comprises 21 289 adult PWH, median age 51.2 years, 82% male, 70% were of Western origin, 12.0% were of sub-Saharan African and 12.6% Latin American/Caribbean origin, 96.8% had HIV-RNA less than 200 copies/ml, median CD4 + cell count 690 (IQR 510-908) cells/μl. Primary SARS-CoV-2 infections were registered in 2301 individuals, of whom 157 (6.8%) required hospitalization and 27 (1.2%) ICU admission. Mortality rates were 13 and 0.4% among hospitalized and nonhospitalized individuals, respectively. Independent risk factors for severe outcomes (COVID-19-related hospitalization and death) were higher age, having multiple comorbidities, a CD4 + cell count less than 200 cells/μl, uncontrolled HIV replication, and prior AIDS diagnosis. Migrants from sub-Saharan Africa, Latin America, and the Caribbean were at an increased risk of severe outcomes independently of other risk factors. CONCLUSION: In our national cohort of PWH, risk of severe COVID-19 outcomes was increased in individuals with uncontrolled HIV replication, low CD4 + cell count, and prior AIDS diagnosis, independently of general risk factors such as higher age, comorbidity burden and migrants originating from non-Western countries.</p