Modulation of Philadelphia Chromosome-Positive Hematological Malignancies by the Bone Marrow Microenvironment

摘要: Hematological malignancies often have cytogenetically distinct chromosomal translocations, resulting in fusion proteins that lead to deregulation of specific signaling pathways and phenotypic outcomes. The constitutively active Bcr-Abl kinase defines the underlying cause for several forms leukemia humans. Due different breakpoints Bcr gene, reciprocal translocation between chromosomes 9 22 (the so-called Philadelphia chromosome (Ph+) (Nowell, 2007; Koretzky, 2007)) generates proto-oncoproteins variable size. p210 protein is predominantly associated with CML during chronic phase, but can also be detected acute lymphoblastic (ALL) blast transformation. In contrast, p185 most generation de novo B-lineage ALL, has been shown expressed rare cases T-cell mast cell as well endothelial cells derived from patients CML. While high, constitutive Abl activity thought driving force initiation progression leukemic disease, bone marrow microenvironment plays a pivotal role maintaining Ph+ stem cells. following chapter we discuss interplay expression microenvironment-derived cues their collective influence on leukemogenesis.