Sujet(s)
Antinéoplasiques/usage thérapeutique , Isocitrate dehydrogenases/génétique , Leucémie aigüe myéloïde/traitement médicamenteux , Leucémie aigüe myéloïde/génétique , Lignage cellulaire , Hématopoïèse/effets des médicaments et des substances chimiques , Hématopoïèse/génétique , Humains , MutationRÉSUMÉ
Human acute myeloid leukemias (AMLs) are sustained by leukemic stem cells (LSCs) that generate through aberrant differentiation the blast cells that make up the bulk of the malignant clone. LSCs were first identified as rare cells with an immunophenotype shared with normal hematopoietic stem cells (HSCs). However, refinements of xenotransplantation assays, alternative methods of quantitation and syngeneic murine models have all led to an appreciation that LSCs display marked variability in frequency, immunophenotype and differentiation potential, both between and even within leukemias. Insights from next-generation sequencing efforts have dramatically extended understanding of the mutational landscape and clonal organization of AML and have added an additional layer of complexity to the biology of LSCs: a requirement to consider the effect of the various recurrently occurring genetic lesions in AML on the initiation and maintenance of leukemic subclones. Despite these advances, cure rates in AML remain substantially unchanged in recent years. A renewed focus on the biological properties of chemotherapy-resistant LSCs, a cellular entity of prime clinical importance, will be required to develop additional therapeutic strategies to enhance patient outcomes.
Sujet(s)
Leucémie myéloïde/anatomopathologie , Syndromes myéloprolifératifs/anatomopathologie , Cellules souches tumorales/anatomopathologie , Animaux , HumainsRÉSUMÉ
This article presents the rationale and methods used to employ hyperbaric oxygen (HBO) treatment for patients with burns at the Sherman Oaks Community Hospital. It is based upon an expanded concept of burn injury formation and healing. We believe that new knowledge of oxygen transport and storage in the tissues in the presence of HBO will alter our understanding of the process of wound healing and the application of HBO in treatment.