Angiogenesis and Microvessel Density in Multiple Myeloma and Other Hematologic Malignancies Prognostic Value and Therapeutic Response

The concept of increased, abnormal tumor vascularity was first put forth and studied in the context of solid tumors.192-198 However, during the last decade increased angiogenesis in the bone marrow has been identified as an important component of hematological malignancies as well. The phenomenon was first described in MM.199 Subsequent studies have demonstrated that angiogenesis is an integral part of the disease biology in almost all hematological malignancies, including acute leukemias, chronic leukemias, lymphomas, mye-lodysplastic syndrome (MDS), and chronic myeloproliferative disorders (Table 4.1). Specifically, increased vascularity was observed in the lymph nodes of B-cell non-Hodgkin's lymphoma (B-NHL)200 and B-cell chronic lymphocytic leukemia (B-CLL)36 201202; as well as in bone marrow (BM) specimens from patients with childhood acute lymphoid leukemia (ALL),203 acute myeloid leukemia (AML),204 chronic myelocytic leukemia (CML),205 MDS,206 and idiopathic myelofibrosis.207 The initial clinical and correlative studies confirmed the prognostic value of angiogenesis in these disorders. For example, in B-NHL BM angio-genesis is highly correlated to tumor grade and the percentage of VEGF-positive cells.208 Furthermore, enhanced BM angiogenesis also has prognostic value in early B-CLL.209

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