The BHD Literature Database has been updated with two articles:
Park et al. show that invariant Natural Killer T (iNKT) cells failed to develop normally in FNIP1-null mice. Although stage 0,1 and 2 cells were found, very few mature stage 3 iNKT cells were found in these mice, suggesting the block happened at some point between stage 2 and stage 3. Additionally, PLZF – which regulates iNKT cell development – was overexpressed in FNIP1-null iNKT cells. Mitochondrial mass was reduced, ATP levels were low, cell size was increased and mTOR signalling was dysregulated in FNIP1-null iNKT cells. BrdU pulse experiments showed that FNIP1-null cells over-proliferated in stage 3 of iNKT cell development, making cells vulnerable to apoptosis, as shown by an increase in Caspase 3-positive cells. Together, this suggests that dysregulated mTOR signalling leads to higher energy consumption, meaning that cells do not have the required energy reserves for proliferation and maturation to stage 3, and die somewhere between stage 2 and 3. However, mTOR dysregulation is not fully responsible for this phenotype, as in vivo treatment of pups, beginning in utero, did not rescue the iNKT cell phenotype.
Kuroda et al. report the pathological findings of kidney tumours from a series of 6 Japanese BHD patients. 5 patients had multifocal tumours, 2 had bilateral tumours and 1 patient had a solitary tumour. The tumour series consisted of 1 unclassified tumour; 3 hybrid oncocytic/chromophobe tumours; 1 collision tumour consisting of chromophobe; clear cell and papillary tumours; a chromophobe tumour; and a clear cell tumour. All tumours had intertumoral peripheral small papillary tufts (ITPSTs) at the interface between the tumour and normal kidney tissue. The authors suggest that ITPSTs might be a diagnostic hallmark of BHD-associated kidney tumours, as they were universal in this cohort of patients.
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