RESUMEN
Invasive mucormycosis is an increasingly common cause of morbidity and mortality in hematologic malignancy patients. Early consideration of the diagnosis is essential in at-risk patients, exhibiting suggestive signs and symptoms. A 56-year-old female with acute myeloid leukemia initially presented with neutropenic fever before subsequently developing dense hemiplegia due to septic emboli to the spine and multifocal abscesses. These findings were later determined to be a result of a disseminated mucor infection and represented a rare manifestation of the disease. Despite the disseminated nature of the infection, identification of the causative organism was initially impeded by limitations in obtaining a tissue sample in a severely thrombocytopenic patient, as is common among hematologic malignancy patients. As a result of this limitation, diagnosis was ultimately made via PCR on bronchiolar lavage fluid. Early consideration of the diagnosis with prompt initiation of treatment is of utmost importance in this invasive infection. Further research is needed to identify and validate rapid, minimally invasive strategies for early diagnosis of mucormycosis.
RESUMEN
DNA double-strand breaks (DSBs) pose a threat to genome stability and are repaired through multiple mechanisms. Rarely, telomerase, the enzyme that maintains telomeres, acts upon a DSB in a mutagenic process termed telomere healing. The probability of telomere addition is increased at specific genomic sequences termed sites of repair-associated telomere addition (SiRTAs). By monitoring repair of an induced DSB, we show that SiRTAs on chromosomes V and IX share a bipartite structure in which a core sequence (Core) is directly targeted by telomerase, while a proximal sequence (Stim) enhances the probability of de novo telomere formation. The Stim and Core sequences are sufficient to confer a high frequency of telomere addition to an ectopic site. Cdc13, a single-stranded DNA binding protein that recruits telomerase to endogenous telomeres, is known to stimulate de novo telomere addition when artificially recruited to an induced DSB. Here we show that the ability of the Stim sequence to enhance de novo telomere addition correlates with its ability to bind Cdc13, indicating that natural sites at which telomere addition occurs at high frequency require binding by Cdc13 to a sequence 20 to 100 bp internal from the site at which telomerase acts to initiate de novo telomere addition.