Angiogenesis in myelodysplastic syndromes

Abstract

SummaryIt is now well established that solid tumour growth depends on angiogenesis. However, less is known about the generation of new vessels in haematological malignancies and, in particular, in preleukaemic-myelodysplastic syndromes (MDS). In this study, bone marrow microvessel density (MVD) was assessed by immunohistochemistry and compared in trephine biopsies from 14 controls, five infectious disease (ID), 82 MDS, 15 acute myeloid leukaemia (AML) and 14 myeloproliferative disorder (MPD) patients. Statistical analysis (P < 0.001) demonstrated that MDS MVD was higher than in controls and ID (21 ± 9 vs 6 ± 2 and 10 ± 8 respectively) but lower than AML (30 ± 12) and MPD (40 ± 12). Among MDS-FAB subtypes, MVD was significantly higher in RAEB-t, CMML and fibrosis subsets compared to RA, RARS and RAEB subsets (P = 0.008). To further investigate angiogenesis machinery, the expression of vascular endothelial growth factor (VEGF) was evaluated by means of immunohistochemistry in control, MDS, AML and MPD biopsies. Even though VEGF mRNA expression was reported in the past in AML cell cultures and cell lines, in our samples VEGF expression was found to be particularly strong in most of the megakaryocytes but significantly less prominent in other cell populations including blasts. Since our findings suggest a correlation between angiogenesis and progression to leukaemia, additional work is now warranted to determine what regulates the generation of new vessels in MDS and leukaemia.

Chronic idiopathic myelofibrosis: independent prognostic importance of bone marrow microvascular density evaluated by CD105 (endoglin) immunostaining

“…4 In addition to the well-established role of angiogenesis in solid tumors, 4 the increase in tumor vascularity has been previously investigated in a variety of hematological neoplasms, including acute lymphatic 15 and myeloid 16,17 leukemias, myelodysplastic syndromes, 14,18 Hodgkin's disease, 19 myeloma, 20-25 lymphoproliferative disorders, 26-31 systemic mastocytosis 32 and chronic myeloproliferative disorders, 5,14 including CIMF. 8 The number of small vessels in a tumor, or MVD, is considered a surrogate indicator of angiogenesis.…”

“…Of these, CD34 appears preferable to CD31 and vWF in Endoglin in myelofibrosis M Ponzoni et al patients with myeloid disorders because of its strong immunoreactivity with endothelial cells and its limited nonvascular expression. 14,21,22 The value of CD34 for assessment of MVD in myeloproliferative disorders, including CIMF, has been demonstrated in recent studies. 8,33 Our study shows that CD105 is also an effective tool for staining bone marrow microvessels and …”

“…Large vessels spanning two adjacent fields were counted only once. We modified our previous experience in visual microvessel scoring 14 as follows: instead of choosing an arbitrary number of fields as previously published, all fields of the whole section were counted at  200 microscopic magnification and a final average MVD value for the whole section was registered. The described modification was introduced in order to avoid the bias of selecting areas with more abundant and/or more intensely stained microvessels.…”

“…Variations in immunostaining technique, such as the use of different primary antibodies among different laboratories, may be one factor. In contrast with Mesa et al, 8 who employed the clone HPCA-1 for CD34 immunostaining, we used the QBEND/10 clone, which has been extensively utilized by our group and other investigators to assess MVD 14,16,24,34 In addition, in our study, a different approach for MVD evaluation was used. Instead of numbering semiquantitatively vessels as done by Mesa et al, 8 we performed a complete count of all vessels in each section.…”

Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma

“…Evidence supporting a role for neoangiogenesis in haematological malignancies has been found in lymphoid (Perez-Atayde et al, 1997; Kini et al, 1998;Veiga et al, 1998) and myeloid leukaemias (Fiedler et al, 1997;Shami et al, 1998;Pruneri et al, 1999), myeloproliferative disorders, myelodysplasia (Aguayo et al, 1998;Pruneri et al, 1999) and myeloma (Vacca et al, 1994(Vacca et al, , 1999aRaza et al, 1999). In non-Hodgkin's lymphomas, expression of angiogenic factors in cell lines (Bellamy et al, 1999) and tissue (Doussis-Anagnostopoulou et al, 1997;Foss et al, 1997;Turley et al, 1998) has been demonstrated.…”