New techniques are on the horizon for the detection of small leukemic clones in both, acute leukemias and myeloproliferative disorders. A promising approach is based on digital polymerase chain reaction (PCR). Digital PCR (dPCR) is a breakthrough technology designed to provide absolute nucleic acid quantification. It is particularly useful to detect a low amount of target and therefore it represents an alternative method for detecting measurable residual disease (MRD). The main advantages are the high precision, the very reliable quantification, the absolute quantification without the need for a standard curve, and the excellent reproducibility. Nowadays the main disadvantages of this strategy are the costs that are still higher than standard qPCR, the lack of standardized methods, and the limited number of laboratories that are equipped with instruments for dPCR. Several studies describing the possibility and advantages of using digital PCR for the detection of specific leukemic transcripts or mutations have already been published. In this review we summarize the available data on the use of dPCR in acute myeloid leukemia and myeloproliferative disorders.

SUMMARY Objectives The purpose of this study was to correlate acute invasive fungal rhinosinusitis (AIFRS) and chronic invasive fungal rhinosinusitis with underlying diseases, aetiological microorganisms, clinical symptoms, radiological findings, and surgical and medical treatment to determine the subset of patients who require more accurate diagnostic investigation and to prevent irreversible complications. Methods This retrospective monocentric study included 17 patients who underwent endoscopic sinus surgery evaluated by paranasal computed tomography and magnetic resonance imaging. Age, sex and symptoms, and location of the invasive fungal infection and the causative fungus were analysed. Results In total, 4 patients were affected by the AIFRS form, and 13 by the chronic form. Diabetes mellitus was reported in 41.17% of cases, and haematological diseases in 23.52%. The maxillary sinuses were involved in 47.05% of cases and sphenoidal sinuses in 52.94%; Aspergillus fumigatus was the fungus in 76.47% of cases, and Zygomycetes in 23.53%. Conclusions An understanding of the different types of fungal sinusitis and knowledge of their features play a crucial role in reaching prompt diagnosis and initiation of appropriate therapy, which is essential to avoid a protracted or fatal outcome.

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Iron is crucial to satisfy several mitochondrial functions including energy metabolism and oxidative phosphorylation. Patients affected by Myelodysplastic Syndromes (MDS) and acute myeloid leukemia (AML) are frequently characterized by iron overload (IOL), due to continuous red blood cell (RBC) transfusions. This event impacts the overall survival (OS) and it is associated with increased mortality in lower-risk MDS patients. Accordingly, the oral iron chelator Deferasirox (DFX) has been reported to improve the OS and delay leukemic transformation. However, the molecular players and the biological mechanisms laying behind remain currently mostly undefined. The aim of this study has been to investigate the potential anti-leukemic effect of DFX, by functionally and molecularly analyzing its effects in three different leukemia cell lines, harboring or not p53 mutations, and in human primary cells derived from 15 MDS/AML patients. Our findings indicated that DFX can lead to apoptosis, impairment of cell growth only in a context of IOL, and can induce a significant alteration of mitochondria network, with a sharp reduction in mitochondrial activity. Moreover, through a remarkable reduction of Murine Double Minute 2 (MDM2), known to regulate the stability of p53 and p73 proteins, we observed an enhancement of p53 transcriptional activity after DFX. Interestingly, this iron depletion-triggered signaling is enabled by p73, in the absence of p53, or in the presence of a p53 mutant form. In conclusion, we propose a mechanism by which the increased p53 family transcriptional activity and protein stability could explain the potential benefits of iron chelation therapy in terms of improving OS and delaying leukemic transformation.