Clinicopathologic correlations of bone marrow angiogenesis in chronic myeloid leukemia: a morphometric study

Abstract

Various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemical staining, were evaluated in the bone marrow of 52 patients with chronic myeloid leukemia (CML) in chronic phase, in relation to several clinicopathologic parameters. Twenty control bone marrows and 15 cases of CML in blastic phase were also studied. Microvessel density (MVD), total vascular area (TVA) and several size- and shape-related parameters were quantitated in the region of most intense vascularization using image analysis. Overall, the group of chronic phase CML had higher MVD and size-related parameters and more branching microvessels than controls. Blastic phase was characterized by increased numbers of microvessels with a rounder shape and smaller caliber than chronic phase. A positive correlation emerged between marrow fibrosis and MVD as well as between white blood cell counts and rounder vessel sections. No relationship existed between microvascular parameters and Hasford or Sokal prognostic scores. In univariate analysis, overall and progression-free survival were adversely affected by MVD, size-related parameters, increased platelet count, age and spleen size. Multivariate analysis indicated that microvessel area was related to progression-free survival, whereas both MVD and area were significant prognosticators of overall survival, even when Hasford or Sokal scores are introduced into the model. Our data suggest that changes in angiogenic parameters may participate in the conversion of normal marrow to CML and ultimately to blastic transformation. More importantly, MVD and microvessel caliber are significant predictors of patient survival and progression.

Angiogenesis in Hodgkin's lymphoma: a morphometric approach in 286 patients with prognostic implications

“…8,11 Briefly, immunohistochemically stained slides for CD34 were scanned, field per field, at  100 magnification, to identify the region showing the most intense vascularization ('hot spot') 7,25 ( Figure 1). In cases including remnants of normal tissue (eg interfollicular HL), these areas were shielded to ensure that microvessel counting was performed in neoplastic tissue.…”

“…5 A plethora of investigations support the intuitive notion that solid tumors progress in concert with an induction of neovascular response (for a review see Hlatky et al 6 ). Evidence of the importance of angiogenesis in hematologic malignancies is rapidly accruing, indirectly implicating bone marrow angiogenesis in the pathophysiology and course of acute leukemias, 7 chronic myeloid and lymphoid leukemias, [8][9][10] myelodysplastic syndromes 11 and multiple myeloma. 12,13 In non-Hodgkin's lymphomas (NHL) and B chronic lymphocytic leukemia, microvessel counts correlate with histologic grade and clinical stage, respectively.…”

Effect of allogeneic stem cell transplantation on bone marrow angiogenesis in chronic myelogenous leukemia

“…Previous studies have demonstrated the presence of increased bone marrow angiogenesis in patients with CML. [12][13][14][15] As in the other hematological malignancies with a similar finding, increased bone marrow angiogenesis appears to have prognostic value in CML, predicting both progression and survival. 14 Malignant cells in CML may have a direct role in the formation of these new blood vessels, and studies suggest that inhibition of angiogenesis may at least in part explain the mechanism of action of drugs used in CML.…”

“…[12][13][14][15] As in the other hematological malignancies with a similar finding, increased bone marrow angiogenesis appears to have prognostic value in CML, predicting both progression and survival. 14 Malignant cells in CML may have a direct role in the formation of these new blood vessels, and studies suggest that inhibition of angiogenesis may at least in part explain the mechanism of action of drugs used in CML. 25 Although new biological agents like imatinib mesylate can result in dramatic clinical improvement in patients with CML, allogeneic stem cell transplant is the only modality that has resulted in a cure and long-term disease-free survival.…”

“…16,32 However, several studies have demonstrated increased bone marrow angiogenesis in patients with CML. 12,14,15 In a study evaluating bone marrow vascularity in acute and chronic leukemias, patients with CML had the highest degree of marrow angiogenesis compared to CLL, acute myeloid and lymphoid leukemias and MDS, other disease states that have been associated with increased marrow angiogenesis. 12 Other studies have shown an increase in the marrow angiogenesis, corresponding to the clinical progression from chronic phase to blastic phase of CML.…”