Concise review: Leukemia stem cells in personalized medicine.
Despite increased comprehension of acute myelogenous leukemia (AML) pathogenesis, current treatment strategies have done little to improve upon standard induction chemotherapy to induce long-term remissions. Since the identification of the leukemic stem cell, efforts have been placed on identifying therapeutically actionable pathways that distinguish this increasingly important cellular compartment. With the advent of increased genome sequencing efforts and phenotypic characterization, opportunities for personalized treatment strategies are rapidly emerging. In this review, we highlight recent advances in the understanding of leukemic stem cell biology and their potential for translation into clinically relevant therapeutics. NF-kappa B activation, Bcl-2 expression, oxidative and metabolic state, and epigenetic modifications all bear their own clinical implications. With advancements in genetic, epigenetic, and metabolic profiling, personalized strategies may be feasible in the near future to improve outcomes for AML patients.
Division of Hematology/Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, New York, USA.
Monica L
ML
Guzman
John N
JN
Allan
D000818:Animals; D044127:Epigenesis, Genetic / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D015894:Genome, Human; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics
D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2
Acute myelogenous leukemia; Hematopoietic stem cells; Leukemia stem cells; Molecular targeted therapies; Translational medicine