Hematopoietic stem cells progressively deficient of glycogen synthase kinase initiate a pre-neoplastic state required for evolution to acute leukemia

ABSTRACT: The cellular origin and molecular progression towards aggressive cancers such as acute myeloid leukemia (AML) remain elusive. Clinically, Myelodysplastic syndromes (MDS) and related myeloproliferative neoplasias (MPN) disorders1-5 are believed to present as a precursor stage to lethal AML development. Despite the identification of cytogenetic abnormalities and increased activation of signaling in human MDS/MPN, specific pathways that either sustain or initiate disease progression and evolve into self-sustaining leukemic-initiating cells (L-ICs)13 have not been elucidated. Here we demonstrate that tissue specific loss of glycogen synthase kinase-3β (GSK3 betaβ) initiates the emergence of stable Pre-leukemic-ICs (PLIC) in vivo. In contrast to deletion or transgenic perturbation of pathways

ORGANISM(S): Mus musculus

SUBMITTER: Mickie Bhatia 

PROVIDER: E-GEOD-53352 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress