Leukemia & Lymphoma, June 2011; 52(S2): 91–93
Hairy cell leukemia and the microenvironment
JOHN C. CAWLEY Division of Haematology, University of Liverpool, Liverpool, UK
Abstract Two-way interactions between HCs and the microenvironment are especially prominent in HCL. Many of these interactions are now reasonably well understood and are summarised in this article.
Keywords: Accessory cells, cytokines, extracellular matrix, HCL, microenvironment Introduction
In all cancers, there is a complex two-way interaction between the malignant cells and their microenviron- ment. Thus, tumor cells alter their surrounding tissues in different ways and, conversely, the microenviron- ment affects the behavior of the malignant cells. Many of these processes are mediated by cytokines produced by both malignant and stromal cells and by adhesive interactions between the malignant cells and their microenvironment. These interactions are, in turn, influenced by the intrinsic oncogenic event(s) respon- sible for malignant transformation (Figure 1). In hairy cell leukemia (HCL), these two-way
interactions are particularly prominent and distinc- tive, and are responsible for much of the pathophy- siology of the disease.
Effects of hairy cells on the microenvironment
Hairy cells (HCs) are highly activated cells. This activation is a consequence of stimulation by the unknown oncogenic event(s) responsible for the disease, as well as the result of signals induced by autocrine and paracrine cytokines and by adhesive interactions with the microenvironment. As a result of their activation, HCs spontaneously produce a range of cytokines and have intrinsically
activated adhesion receptors. Many of these cyto- kines and their effects have now been well character- ized (reviewed in [1]). The intrinsically activated adhesion receptors of
HCs and some of their effects have also been well characterized (Table I and reviewed in [1]). For example, the interaction of the integrin heterodimer, a4b1, with its ligand, vascular cell adhesion molecule (VCAM), probably plays a major role in the formation of the splenic pseudosinuses [2] that are pathognomonic of the disease.
Effects of the microenvironment on hairy cells
The microenvironment influences many aspects of HC behavior, including cell survival, motility/inva- sion, and cytokine production. Regarding cell survival, adhesion interactions with
accessory cells and matrix have anti-apoptotic effects. For example, integrin engagement by fibronectin (FN) or vitronectin protects HCs from the killing effects of interferon; such integrin stimulation acts via preventing the reduction of inhibitors of apoptosis (IAPs) by interferon [3]. With regard to motility and the related phenom-
enon of tissue invasion, engagement of the integrin heterodimer avb3 on HCs stimulates cell motility, and this interaction is probably important in the
Correspondence: Prof. John C. Cawley, Division of Haematology, University of Liverpool, 3rd Floor, Duncan Building, Daulby Street, Liverpool L69 3GA, UK. E-mail:
J.cawley@
liv.ac.uk
ISSN 1042-8194 print/ISSN 1029-2403 online 2011 Informa UK, Ltd. DOI: 10.3109/10428194.2011.570393
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