Secondary solid cancer screening following hematopoietic cell transplantation.

Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.

RNA turnover and the control of mitochondrial gene expression.

Recent evidence suggests that RNA turnover in yeast mitochondria is important, not only to regulate RNA abundance, but also to facilitate group I intron splicing and suppress the potentially toxic effect of high levels of excised group I intron RNAs. Protein-assisted splicing of group I introns requires that splicing factors are 'actively' recycled, because of their tight binding to the intron RNA. The putative NTP-dependent RNA helicase Suv3p might promote this recycling and, at the same time, suppress intron overaccumulation because of the functional association of this protein with mtEXO, a novel 3'-5' exoribonuclease that can degrade excised group I intron RNAs.

The DExH box protein Suv3p is a component of a yeast mitochondrial 3'-to-5' exoribonuclease that suppresses group I intron toxicity.

The yeast mitochondrial protein Suv3p is a putative NTP-dependent RNA helicase. Here we report that in cells lacking Suv3p, there is an approximately 50-fold increase in the excised form of the group I intron omega of the mitochondrial 31S rRNA gene. Surprisingly, little mature 21S rRNA accumulates in those cells; instead, unligated 21S rRNA exons appear. Intron overaccumulation could lead to spliced exon reopening via a reaction known to be catalyzed by group I introns in vitro. We also show that Suv3p is a functional component of a novel mitochondrial NTP-dependent 3'-to-5' exoribonuclease activity that can degrade group I intron RNAs. These findings account for group I intron overaccumulation in cells lacking Suv3p and define a novel function for putative RNA helicases in direct RNA degradation.

The yeast nuclear gene suv3 affecting mitochondrial post-transcriptional processes encodes a putative ATP-dependent RNA helicase.

Mitochondrial gene expression is controlled largely through the action of products of the nuclear genome. The yeast nuclear gene suv3 has been implicated in a variety of mitochondrial posttranscriptional processes and in translation and, thus, represents a key control element in nuclear-mitochondrial interactions. We have exploited a property of a mutant allele of suv3, SUV3-1, that causes, among other effects, a massive increase in the abundance of excised group I introns to clone the wild-type gene by a strategy of colony Northern hybridization. We have determined that the 84-kDa deduced protein product of the suv3 gene, which maps to chromosome XVI, has a typical mitochondrial targeting presequence and additional sequence motifs that suggest that it belongs to a family of ATP-dependent RNA helicases, enzymes whose importance in post-transcriptional and translational events has recently become apparent. We have identified the SUV3-1 mutation as a G----T transversion that creates a Val----Leu substitution in a 10-amino acid block that is highly conserved among ATP-dependent RNA helicases. We discuss some implications of this mutation on the effects of the SUV3-1 allele on mitochondrial RNA metabolism.