Reversal of MYB-dependent suppression of MAFB expression overrides leukaemia phenotype in MLL-rearranged AML.

The transcription factor MYB plays a pivotal role in haematopoietic homoeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). We have previously demonstrated that not all AML subtypes display the same dependency on MYB expression and that such variability is dictated by the nature of the driver mutation. However, whether this difference in MYB dependency is a general trend in AML remains to be further elucidated. Here, we investigate the role of MYB in human leukaemia by performing siRNA-mediated knock-down in cell line models of AML with different driver lesions. We show that the characteristic reduction in proliferation and the concomitant induction of myeloid differentiation that is observed in MLL-rearranged and t(8;21) leukaemias upon MYB suppression is not seen in AML cells with a complex karyotype. Transcriptome analyses revealed that MYB ablation produces consensual increase of MAFB expression in MYB-dependent cells and, interestingly, the ectopic expression of MAFB could phenocopy the effect of MYB suppression. Accordingly, in silico stratification analyses of molecular data from AML patients revealed a reciprocal relationship between MYB and MAFB expression, highlighting a novel biological interconnection between these two factors in AML and supporting new rationales of MAFB targeting in MLL-rearranged leukaemias.

Cardiac magnetic resonance in systemic sclerosis patients with cardiac symptoms.

OBJECTIVE: Systemic sclerosis (SSc) is characterized by widespread vascular lesions and skin and internal organs fibrosis, including the heart; all cardiac layers, endocardium, myocardium, and pericardium, may be involved. We report the relevance of cardiac MRI findings in scleroderma patients with cardiac symptoms. PATIENTS AND METHODS: 50 patients, all fulfilling the ACR SSc criteria (19 with limited and 31 with diffused skin involvement) were evaluated using a 1.5T MR scanner. Images were acquired before and after contrast medium administration; the exams were considered positive with one or more of these findings: enlarged volumes, reduced EF, regional kinetic anomalies, edema, DE or pericardial effusion. RESULTS: 40 patients (80%) had one or more cardiac abnormalities: 5 patients had myocardial edema; 2 an increased interventricular septum thickness; 22 dilated ventricles or reduced EF; 12 an abnormal regional ventricular motion (2 of these with akinetic segments); 17 a delayed enhancement with different patterns, all without coronary distribution; 22 a pericardial effusion CONCLUSIONS: Pathologic findings were documented in 80% of the cases confirming a high occurrence of abnormal MR data. Myocardial involvement in systemic sclerosis can be assumed by the presence of multiple pathologic MRI findings. CMR seems to be a valuable tool to identify and assess the presence of cardiac involvement.

Seasonal concordance of recurrence in mood disorder patients.

The aim of the present study is to evaluate the seasonal pattern of recurrences and the concordance among first episode (index episode) versus the subsequent recurrences in a sample of 210 patients affected by mood disorders, referred to the Mood Disorder Unit of San Raffaele Hospital. The most depressive recurrences are in spring for unipolar subjects and in fall for bipolars. Manic episodes are more frequent in summer. Patients presented a high concordance rate between the first and the second episode, female patients were more concordant than male subjects, and patients with low cycle of illness (one episode every six or more years) were the most concordant ones.