RESUMO
Formal training or education, in pedagogy in library school or as part of job onboarding process, remains sparse, despite being a required qualification for a significant portion of academic librarian positions. This situation often leaves early career librarians left to piece together their knowledge of effective teaching strategies. This article discusses the experience of an early career librarian in learning pedagogical practices as well as the specific needs of a new discipline. Considerations of barriers, such as imposter syndrome and what the librarian wishes had gone differently, are covered.
Assuntos
Bibliotecários , Bibliotecas Médicas , Transtornos de Ansiedade , Humanos , Aprendizagem , AutoimagemRESUMO
Enrichment of leukemic blasts with a stem cell phenotype correlates with poor survival in acute myeloid leukemia (AML). In this context, measurement of the stem cell marker aldehyde-dehydrogenase (ALDH) activity can distinguish poor prognosis cases with increased fractions of ALDH-positive cells (ALDH-numerous AML) and favorable outcome cases with low percentages (ALDH-rare AML). It has been shown that ALDH-numerous AML favor leukemic engraftment in xenotransplantation assays which suggests increased leukemic stem cell (LSC) potential. To test if this reflects an immature cell of origin, comparative gene-expression studies of CD34+ leukemic blasts were performed. This analysis revealed increased expression of LSC and HSC signatures in ALDH-numerous AML, whereas ALDH-rare AML were enriched for a progenitor signature. The enrichment of stemness-associated transcriptional programs suggests that ALDH-numerous AML derive from immature hematopoietic progenitors and offers an explanation for the poor prognosis and therapy resistance of this subgroup which is likely caused by inherited stem cell properties.
Assuntos
Aldeído Desidrogenase/genética , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Leucemia Mieloide Aguda/genética , Células-Tronco Neoplásicas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Aldeído Desidrogenase/metabolismo , Animais , Antígenos CD34/metabolismo , Biomarcadores Tumorais/metabolismo , Linhagem da Célula/genética , Feminino , Células-Tronco Hematopoéticas/enzimologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/metabolismo , Masculino , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/enzimologia , Transplante HeterólogoRESUMO
In patients with acute myeloid leukemia and low percentages of aldehyde-dehydrogenase-positive cells, non-leukemic hematopoietic stem cells can be separated from leukemic cells. By relating hematopoietic stem cell frequencies to outcome we detected poor overall- and disease-free survival of patients with low hematopoietic stem cell frequencies. Serial analysis of matched diagnostic and follow-up samples further demonstrated that hematopoietic stem cells increased after chemotherapy in patients who achieved durable remissions. However, in patients who eventually relapsed, hematopoietic stem cell numbers decreased dramatically at the time of molecular relapse demonstrating that hematopoietic stem cell levels represent an indirect marker of minimal residual disease, which heralds leukemic relapse. Upon transplantation in immune-deficient mice cases with low percentages of hematopoietic stem cells of our cohort gave rise to leukemic or no engraftment, whereas cases with normal hematopoietic stem cell levels mostly resulted in multi-lineage engraftment. Based on our experimental data, we propose that leukemic stem cells have increased niche affinity in cases with low percentages of hematopoietic stem cells. To validate this hypothesis, we developed new mathematical models describing the dynamics of healthy and leukemic cells under different regulatory scenarios. These models suggest that the mechanism leading to decreases in hematopoietic stem cell frequencies before leukemic relapse must be based on expansion of leukemic stem cells with high niche affinity and the ability to dislodge hematopoietic stem cells. Thus, our data suggest that decreasing numbers of hematopoietic stem cells indicate leukemic stem cell persistence and the emergence of leukemic relapse.