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SLC25A51 selectively imports oxidized NAD+ into the mitochondrial matrix and is required for sustaining cell respiration. We observed elevated expression of SLC25A51 that correlated with poorer outcomes in patients with acute myeloid leukemia (AML), and we sought to determine the role SLC25A51 may serve in this disease. We found that lowering SLC25A51 levels led to increased apoptosis and prolonged survival in orthotopic xenograft models. Metabolic flux analyses indicated that depletion of SLC25A51 shunted flux away from mitochondrial oxidative pathways, notably without increased glycolytic flux. Depletion of SLC25A51 combined with 5-azacytidine treatment limits expansion of AML cells in vivo. Together, the data indicate that AML cells upregulate SLC25A51 to decouple mitochondrial NAD+/NADH for a proliferative advantage by supporting oxidative reactions from a variety of fuels. Thus, SLC25A51 represents a critical regulator that can be exploited by cancer cells and may be a vulnerability for refractory AML. [Display omitted] • Elevated SLC25A51 expression correlates with poorer outcomes in patients with AML • AML cells rely on a SLC25A51-dependent oxidative NAD+/NADH ratio for tumorigenesis • Its loss targets the oxidative mitochondrial compartment in vulnerable cell types • SLC25A51 depletion combines with 5-azacytidine to limit AML cell expansion NAD+ is essential for oxidative metabolism. Lu et al. show that acute myeloid leukemic cells upregulate mitochondrial NAD+ transporter, SLC25A51, to support an oxidative NAD+/NADH ratio specifically in this compartment for a proliferative advantage. Depletion of SLC25A51 reduced tumor burden in orthotopic xenograft models. [ABSTRACT FROM AUTHOR]

Objective: To explore the knowledge and attitudes toward preimplantation genetic diagnosis (PGD) of women who have been personally affected by hereditary breast and ovarian cancer. Design: A 33-item quantitative survey covering five domains, including demographics, knowledge and attitudes about PGD, usage of PGD, and informational needs. Setting: Attendees of a national conference for individuals and families affected by hereditary breast and ovarian cancer participated in the survey. Patient(s): Not applicable. Intervention(s): Not applicable. Main Outcome Measure(s): Frequencies and proportions were summarized for all variables, and Fisher''s exact tests were conducted to test association between two discrete variables. Result(s): Of the women surveyed, only 32% had ever heard of PGD before taking the survey. None of the women surveyed had actually used PGD, and 44% believed they would not use it in the future. However, 57% of attendees believed that PGD was an acceptable option for high-risk individuals, and 74% believed that high-risk individuals should be given information about PGD. Conclusion(s): Health care professionals who serve cancer patients should consider incorporating information about PGD into patient education. Further research is needed to survey physicians and genetic counselors about their knowledge and opinions of PGD. [Copyright &y& Elsevier]

Objective: This study sought to determine if physician's personal discomfort with the topic of FP and a patient's prognosis would have an impact on the likelihood of discussing FP with cancer patients. Methods: Data from larger studies of qualitative semi-structured interviews with pediatric and adult oncologists were analyzed using grounded theory and crystallizing immersion method to examine the themes of “personal comfort” and “patient prognosis” in relation to discussion. Results: Results showed that, across both physician types, the majority of respondents’ personal comfort with the topic of FP was related to the likelihood of discussion. Personal discomfort manifested as: (a) lack of knowledge; (b) language/cultural barriers; (c) perception that subject of FP adds more stress to situation; (d) general uncertainty about success of FP methods. Data also indicate physicians do not feel discussions are appropriate for patients with poor prognosis. Conclusion: Despite the ASCO guidelines suggesting physicians should discuss FP with all patients, the majority of physicians are not following these guidelines. Practice implications: Improved training on recognition of such biases and communication strategies may improve the quality and frequency of such discussions. Involving the entire healthcare team in discussions may alleviate the need for physicians to have sole responsibility. [Copyright &y& Elsevier]

Abstract: Objective: Limited research has been conducted on the extent to which fertility preservation is discussed by pediatric oncologists with patients and less is known about the discussion content. This study sought to examine factors that may influence the discussion with pediatric cancer patients and families. Methods: Qualitative data were collected using open-ended, in-depth interviews with 24 pediatric oncologists in Florida at 13 children''s cancer centers, representing 87% of the centers in the state. Results: Providers practiced between 0.5 and 35 years, treated most types of pediatric cancers, and most were board certified in pediatric hematology/oncology. The main factors associated with a discussion of fertility preservation options were: (1) physician factors that contribute to communication issues with FP discussion (e.g., awareness and sense of comfort in discussing issues, perceptions of the priority); (2) parent factors (e.g., receptiveness and cultural background); (3) patient factors (e.g., receptiveness and age); and (4) institutional factors (e.g., referral sites and practice guidelines). Conclusions: Pediatric oncologists may benefit from education about fertility preservation options for pediatric cancer patients, particularly females. Practice implications: Training on how to address parents’ and patients’ emotions, culture, and other factors may also promote the discussion. Although guidelines have been established, barriers related to availability and affordability of resources must also be addressed. [Copyright &y& Elsevier]