Haemopoietic growth factor tyrosine kinase receptor expression profiles in normal haemopoiesis

Abstract

Expression profiles were generated for the haemopoietic tyrosine kinase receptors (HGF-TKRs or class III TKRs) by PCR on cDNA samples (RT-PCR) using a degenerate primer set. Each profile consisted of primary and secondary, i.e. enriched for less-expressed sequences, fingerprints. This method was applied on FACS-purified haemopoietic CD34+ cells, both from bone marrow (BM) and umbilical cord blood (UCB), and on mature cells from peripheral blood. CD34+ BM cells showed expression of c-fms. flt3, whereas CD34+ UCB cells expressed c-fms and, to a lesser extent, c-kit and flt3. In mature blood cells, only c-fms was observed in monocytes and a weaker flt3 expression in monocytes and T lymphocytes, whereas no known class III TKRs were detected in B lymphocytes and polymorphonuclear cells (PMNs). In all fractions a novel band could be observed, which appeared to be RET. Expression of RET was confirmed by RT-PCR and showed the highest levels in monocytes, followed by PMNs and CD34+ cells. B lymphocytes revealed low levels of expression. RET is known to be essential in neural development. Our results suggest a possible role for this receptor in haemopoiesis.

Immunostimulatory effect of Fms-like tyrosine kinase 3 ligand on peripheral monocyte-derived dendritic cells and natural killer cells: Utilization for ovarian cancer treatment

“…In contrast, the in vitro effects of FLT3L on mature peripheral blood cells have received less attention (41). It is believed that FLT3 expression is confined mainly to progenitor cells, and its expression has not been observed in monocytes in the physiological condition (8)(9)(10). In accordance with these previous reports, we did not detect expression of FLT3 in purified peripheral monocytes.…”

“…As previously reported (8)(9)(10)(11), no detectable FLT3 expression was observed in peripheral blood CD14 + monocytes by flow cytometry. (Fig.…”

“…To date, the function of FLT3L has mainly been examined in hematopoietic progenitor cells, as FLT3 is expressed almost exclusively in hematopoietic progenitor cells (8)(9)(10)(11). FLT3L is known to cause proliferation of hematopoietic stem cells in vitro (12,13) and as a result, systemic administration of soluble FLT3L, which increases circulating numbers of dendritic cells (DCs) and natural killer (NK) cells, enhances anti-tumoral and viral immunity in vivo (3,(14)(15)(16).…”

Expression and alternative splicing of c-ret RNA in papillary thyroid carcinomas

“…RT ± PCR results could be in¯uenced by c-ret mRNA contamination from stromal cells, lymphocytes (Visser et al, 1996), or parafollicular C-cells in normal thyroid tissue. These sources of ret transcripts are, however, unlikely as an explanation for the observed cret mRNA in papillary carcinomas since in situ hybridization did not show evidence of ret mRNA expression in lymphocytes or stromal cells (Lam et al, The notation of two temperatures (e.g.…”

The RET receptor tyrosine kinase, but not its specific ligand, GDNF, is preferentially expressed by acute leukaemias of monocytic phenotype and is up-regulated upon differentiation

“…the glial cell line-derived neurotrophic factor (GDNF) (Jing et al, 1996;Treanor et al, 1996) and the neurturin (NTN) (Kotzbauer et al, 1997). Recent studies have shown that GDNF-and NTN-dependent RET signalling requires the presence of either one of two related glycosyl-phosphatidylinositol (GPI)-linked cell surface-associated co-receptors, respectively termed GDNFR-a (Jing et al, 1996;Treanor et al,Although first described as a non-haemopoietic RTK involved in the physiologic development of neural crest derivatives, enteric nervous system and components of the excretory system Pichel et al, 1996;Sanchez et al, 1996), previous studies from our and other groups (Visser et al, 1996;Gattei et al, 1997a) have demonstrated the expression of the RET RTK in human normal and malignant haemopoietic cells. In particular, RET mRNA, expressed at a low level in normal CD34 þ haemopoietic progenitors, has been found to increase upon differentiation to mature myelomonocytic cells, being maximal in circulating neutrophils and monocytes (Visser et al, 1996;Gattei et al, 1997a).…”