Extrinsic and intrinsic cues involved in BCR-ABL induced leukemogenesis:Establishing an ectopic humanized niche xenograft model and the study of metabolic alterations in chronic myeloid leukemia

Leukemia is defined as the cancer of blood cells. Any defect in properties of hematopoietic stem cells (HSC) i.e. either in self-renewal or differentiation leads to the development of hematopoietic malignancies. The hematological malignancies are considered to arise from leukemic stem cells (LSCs) [5–7]. LSCs adopt the regulatory machinery of normal HSCs and sequentially acquire genetic alterations, thus contributing to leukemogenesis i.e. development and progression of hematopoietic malignancy [8]. These sequential genetic alterations can affect cells of lymphoid origin leading to the formation of acute lymphocytic leukemia (ALL) or chronic lymphocytic leukemia (CLL) or affect the cells of myeloid origin leading to acute myeloid leukemia (AML) or chronic myeloid leukemia (CML) [9]. Acute refers to the rapid progression of disease while in chronic leukemia disease persists for a long period of time. Cancer of blood also includes multiple myeloma, Hodgkin disease, and non-Hodgkin lymphoma as well. This thesis focuses on modeling of CML in a mouse model based on human bone marrow and the study of increased energy dependency on glutamine in CML cells