Psychosocial Morbidity and its Correlates in Cancer Patients of the Mediterranean Area: Findings from the Southern European Psycho-Oncology Study

BACKGROUND: A few and partial data are available on psychosocial morbidity among cancer patients in Mediterranean countries. As a part of a more general investigation (Southern European Psycho-Oncology Study-SEPOS), the rate of psychosocial morbidity and its correlation with clinical and cultural variables were examined in cancer patients in Italy, Portugal and Spain. METHODS: A convenience sample of cancer outpatients with good performance status and no cognitive impairment were approached. The Hospital Anxiety-Depression scale (HAD-S), the Mini-Mental Adjustment to Cancer scale (Mini-MAC), and the Cancer Worries Inventory (CWI) were used to measure psychological morbidity, coping strategies and concerns about illness. RESULTS: Of 277 patients, 34% had pathological scores ("borderline cases" plus "true cases") on HAD-S Anxiety and 24.9% on HAD-S Depression. Total psychiatric "caseness" was 28.5% and 16.6%, according to different HAD cut-offs (14 and 19, respectively). Significant relationships of HAD-S Anxiety, HAD-S Depression, HAD-S Total score, with Mini-MAC Hopeless and Anxious Preoccupation, and CWI score were found. No differences emerged between countries on psychosocial morbidity, while some differences emerged between the countries on coping mechanisms. Furthermore, Fatalism, Avoidance and marginally Hopeless were higher compared to studies carried out in English-speaking countries. LIMITATIONS: The relatively small sample size and the good performance status prevent us to generalize data on patients with different cancer sites and advanced phase of illness. CONCLUSIONS: One-third of the patients presented anxiety and depressive morbidity, with significant differences in characteristics of coping in Mediterranean countries in comparison with English-speaking countries.

Adult B-Cell Acute Lymphoblastic Leukemia Cells Display Decreased PTEN Activity and Constitutive Hyperactivation of PI3K/Akt Pathway Despite High PTEN Protein Levels

Adult B-cell acute lymphoblastic leukemia remains a major therapeutic challenge, requiring a better characterization of the molecular determinants underlying disease progression and resistance to treatment. Here, using a phospho-flow cytometry approach we show that adult diagnostic B-cell acute lymphoblastic leukemia specimens display PI3K/Akt pathway hyperactivation, irrespective of their BCR-ABL status and despite paradoxically high basal expression of PTEN, the major negative regulator of the pathway. Protein kinase CK2 is known to phosphorylate PTEN thereby driving PTEN protein stabilization and concomitant PTEN functional inactivation. In agreement, we found that adult B-cell acute lymphoblastic leukemia samples show significantly higher CK2 kinase activity and lower PTEN lipid phosphatase activity than healthy controls. Moreover, the clinical-grade CK2 inhibitor CX-4945 (Silmitasertib) reversed PTEN levels in leukemia cells to those observed in healthy controls, and promoted leukemia cell death without significantly affecting normal bone marrow cells. Our studies indicate that CK2-mediated PTEN posttranslational inactivation, associated with PI3K/Akt pathway hyperactivation, are a common event in adult B-cell acute lymphoblastic leukemia and suggest that CK2 inhibition may constitute a valid, novel therapeutic tool in this malignancy.