Blood, 1 January 2003, Vol. 101, No. 1, pp. 376-376
CORRESPONDENCE
To the editor:
The role of interleukin-3 and stem cell factor in
classical Hodgkin disease
We have read with great interest the comprehensive review by
Skinnider and Mak that summarizes the current literature regarding the
expression and activity of cytokines in classical Hodgkin disease
(cHD), a unique pathologic condition in which a minority of clonal
neoplastic cells are embedded in a heterogeneous background of
nonmalignant cells.1 As stated by the authors,
given the peculiar features of HD, bona fide HD-derived cell lines
remain to date invaluable tools for investigating the
cytokine-dependent interactions of Hodgkin-Reed Sternberg (H-RS)
cells. Nevertheless, information from these studies should be always
confirmed and validated by other studies carried out in the context of
fresh HD-involved tissues or involving primary H-RS cells. By using such an approach, we have described 2 cytokine circuitries allegedly operating in HD that involve interleukin-3 (IL-3), stem cell factor (SCF), and their corresponding receptors (Rs).2-5
As opposed to data reported by Skinnider and
Mak,1 our evidence seems to suggest a role for IL-3 in
H-RS cell proliferation and survival.2 In this regard, we
demonstrated that IL-3 can promote the clonogenic growth of HD-derived
cells and is able to partially rescue them from apoptosis induced by
serum deprivation.2 Accordingly, HD-derived cell lines
express mRNA and protein of the IL-3R
complex, whereas primary
H-RS cells from all cHD cases tested can be stained by anti-IL-3R
antibodies.2
On the other hand, data reported by Skinnider and Mak indicating the
lack of IL-3 production by HD-derived cell lines1 are
consistent with our findings obtained by using a technical approach as
sensitive as reverse transcriptase-polymerase chain reaction.2
Moreover, the notion that IL-3 mRNA was detected by Northern analysis
in some cases of cHD-involved tissues, as reported by Skinnider and
Mak,1 is in keeping with data from our group demonstrating
the ability of HD-derived cells to modulate the production of IL-3 by T
cells.3 In fact, preactivated purified T cells, when
cultured along with paraformaldehyde-fixed HD-derived cells, release
significantly higher amounts of IL-3 than in cultures carried out
without fixed HD-derived cells.3
The expression of SCF receptor (SCFR)/c-kit by the
neoplastic component of cHD has been described by us some years
ago.4 This data, given the notion that fibrosis is a
common feature of cHD-involved tissues6 and SCF is
produced by several stomal cells including fibroblasts,7
strongly suggested a role of SCF/SCFR pair in cHD. The formal proof of
this has been recently provided.5 By using HD-derived cell
lines and fibroblasts from HD-involved lymph nodes (HDF), we
demonstrated the expression of c-kit in HD-derived cells and of SCF in
primary HDF.5 Moreover, functional experiments have shown
the in vitro adhesion of HD-derived cells to HDF through c-kit/SCF
interactions, as well as the capability of SCF to increase the
growth/survival of HD-derived cells, and to partially rescue HD-derived
cells from apoptosis induced by serum starvation.5
To improve the knowledge of the various cytokine pathways sustaining
H-RS cell proliferation and survival may eventually contribute to the
design of innovative therapies for relapsed/refractory HD patients.
Donatella Aldinucci and Valter Gattei
Correspondence: Donatella Aldinucci, Clinical and Experimental
Hematology Research Unit, Centro di Riferimento Oncologico, IRCCS,
Istituto Nazionale Tumori, via Pedemontana Occidentale 12, Aviano
I-33081, Italy; e-mail: daldinucci{at}cro.it
References
1.
Skinnider BF, Mak TW.
The role of cytokines in classical Hodgkin lymphoma.
Blood.
2002;99:4283-4297[Abstract/Free Full Text].
2.
Aldinucci D, Poletto D, Gloghini A, et al.
Expression of functional interleukin-3 receptors on Hodgkin and Reed-Sternberg cells.
Am J Pathol.
2002;160:585-596[Abstract/Free Full Text].
3. Aldinucci D, Gattei V. Functional interleukin-3 receptors in Hodgkin's
disease-derived cell lines. Am J Pathol. In press.
4.
Pinto A, Gloghini A, Gattei V, et al.
Expression of the c-kit receptor in human lymphomas is restricted to Hodgkin's disease and CD30+ anaplastic large cell lymphomas.
Blood.
1994;83:785-792[Abstract/Free Full Text].
5.
Aldinucci D, Poletto D, Nanni P, et al.
Hodgkin and Reed-Sternberg cells express functional c-kit receptors and interact with primary fibroblasts from Hodgkin's disease-involved lymph nodes through soluble and membrane bound-stem cell factor.
Br J Haematol.
2002;118:1055-1064[CrossRef][Medline]
[Order article via Infotrieve].
6.
Gloghini A, Volpe R, Carbone A.
Vimentin immunostaining in fibroblastic reticulum cells within human reactive and neoplastic lymphoid tissues.
Hum Pathol.
1990;21:792-798[CrossRef][Medline]
[Order article via Infotrieve].
7.
Linenberger ML, Jacobson FW, Bennett LG, et al.
Stem cell factor production by human marrow stromal fibroblasts.
Exp Hematol.
1995;23:1104-1114[Medline]
[Order article via Infotrieve].
