Lactate Maintains BCR/Abl Expression and Signaling in Chronic Myeloid Leukemia Cells Under Nutrient Restriction

This study was directed to deepen the effects of nutrient shortage on BCR/Abl_protein expression and signaling in chronic myeloid leukemia (CML) cells. The backbone of the study was cell culture in medium lacking glucose, the consumption of which we had previously shown to drive BCR/Abl_protein suppression, and glutamine, the other main nutrient besides glucose. In this context, we focused on the role of lactate, the main by-product of glucose metabolism under conditions of rapid cell growth, in particular as a modulator of the maintenance of CML stem/progenitor cell potential, a crucial determinant of disease course and relapse of disease. The results obtained indicated that lactate is a powerful surrogate of glucose to prevent the suppression of BCR/Abl signaling and is therefore capable to maintain BCR/Abl-dependent CML stem/progenitor cell potential. A number of metabolism-related functional and phenotypical features of CML cells were also determined. Among these, we focused on the effect of lactate on oxygen consumption rate, the dependence of this effect on the cell surface lactate carrier MCT-1, and the relationship of the lactate effect to pyruvate and to the activity of mitochondrial pyruvate carrier.Key words: Chronic myeloid leukemia (CML), Nutrient shortage, Lactate, Stem cell potential, Acidosis, MCT-1     

Contemporary cardiovascular computed tomography (CCT) training: Serial surveys of the international CCT community by the Fellow and Resident Leaders of the Society of Cardiovascular Computed Tomography (SCCT) Committee (FiRST) and SCCT Future Leaders Program (FLP)

BackgroundAs cardiovascular computed tomography (CCT) practice evolves, the demand for specialists continues to increase. However, CCT training remains variable globally with limited contemporaneous data to understand this heterogeneity. We sought to understand the role of CCT globally and the training available to underpin its use.MethodsWe performed two consecutive surveys of cardiology and radiology physicians, two years apart, utilizing the Society of Cardiovascular Computed Tomography (SCCT) website, weblinks, social media platforms, and meeting handouts to maximize our response rate. We compared United States (US)-based vs. international responses to understand global similarities and differences in practice and training in the surveys.Results235 respondents (37% trainees and 63% educators/non-trainees) initiated the first survey with 174 (74%) completing the core survey, with 205 providing their work location (114 US and 91 international). Eighty-four percent (92/110) of educator respondents stated a need for increased training opportunities to meet growing demand. Dedicated training fellowships are heterogenous, with limited access to structural heart imaging training, despite structural scanning being performed within institutions. The lack of a standardized curriculum was identified as the main obstacle to effective CCT learning, particularly in the US, with web-based learning platforms being the most popular option for improving access to CCT training. 148 trainees initiated the second survey with 107 (72%) completing the core components (51% North America, 49% international). Only 68% said they would be able to meet their required CCT education needs via their training program. Obstacles in obtaining CCT training again included a lack of a developed curriculum (51%), a lack of dedicated training time (35%), and a lack of local faculty expertise (31%). There was regional variability in access to CCT training, and, in contrast to the first survey, most (89%) felt 1:1 live review of cases with trained/expert reader was most useful for improving CCT training alongside formal curriculum/live lectures (72%).ConclusionsThere is a need to expand dedicated CCT training globally to meet the demand for complex CCT practice. Access to CCT education (didactic and 1:1 case-based teaching from expert faculty), implementation of recently published global training curricula, and increased teaching resources (web-based) as an adjunct to existing experiential learning opportunities, are all deemed necessary to address current educational shortfalls.