Regulation of normal and leukemic stem cells through cytokine signaling and the microenvironment.
Leukemias depend on transformed stem cells for their growth and thus these cells represent important therapeutic targets. However, leukemic stem cells resemble normal hematopoietic stem cells (HSCs) with respect to most surface markers, gene expression patterns, and ability to be transplanted. Furthermore, the microenvironment that supports healthy HSCs non-hematopoietic populations, and immune cells correspondingly, the cytokines, adhesion molecules and signal transduction pathways are also impaired during leukemogenesis. This altered environment promotes leukemic growth specifically through pro-inflammatory cytokines. Here, we characterize normal and leukemic signaling, as well as the instructive cues from the neighboring hematopoietic cells and the microenvironment that promote stem cell self-renewal and differentiation.
Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, AL, USA.
Virginia
V
Camacho
Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, AL, USA.
Victoria
V
McClearn
Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, AL, USA.
Sweta
S
Patel
Division of Hematology and Oncology, The University of Alabama at Birmingham, Birmingham, AL, USA. rwelner@uab.edu.|Comprehensive Cancer Center, 1824 6th Ave S, WTI 510D, Birmingham, AL, 35294, USA. rwelner@uab.edu.
Robert S
RS
Welner
D015815:Cell Adhesion Molecules / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016207:Cytokines / Q000502:physiology*; D006412:Hematopoietic Stem Cells; D007938:Leukemia / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D015398:Signal Transduction / Q000502:physiology*; D059016:Tumor Microenvironment / Q000235:genetics
D015815:Cell Adhesion Molecules; D016207:Cytokines
HSC; Leukemia; Microenvironment; Niche