Autocrine and paracrine regulation of neoplastic cell growth in hairy cell leukemia.
Hairy cell leukemia (HCL), a rare haematological disorder of B-cell origin, mainly presents with bone marrow infiltration, haematopoietic insufficiency, and splenomegaly. In some cases, osteolytic lesions can be observed. Many of these clinical features, especially haematopoietic insufficiency and osteolytic lesions are likely to be caused by soluble factors, such as cytokines. There is evidence that these factors are produced by the malignant hairy cells themselves, suggesting a paracrine pathway. The importance of autocrine as well as paracrine growth loops in growth regulation of HCL-cells is supported by a series of excellent studies, performed within the last few years. It could be clearly shown that cytokines are involved in this autocrine and paracrine regulatory process. The most important cytokines which should be mentioned in this respect are tumor necrosis factor alpha, (TNF alpha). Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6) and B-cell-growth factor (BCGF). The role of other factors such as viruses and oncogenes remains rather unclear. Nevertheless, recent data suggest that the c-fms, which encodes for the macrophage colony stimulating factor (M-CSF) may be involved in the pathophysiological control of HCL growth. In this review, we summarise the important data and studies performed recently which shed light on the complex network of autocrine and paracrine growth regulation of HCL.
Schmid
M
M
Department of Internal Medicine III, Haematology and Oncology, University of Ulm, Germany.
Porzsolt
F
F
D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D016298:Hematopoietic Cell Growth Factors / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D007943:Leukemia, Hairy Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009857:Oncogenes; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology
D016207:Cytokines; D016298:Hematopoietic Cell Growth Factors; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha