Bone marrow angiogenesis: methods of quantification and changes evolving in chronic myeloproliferative disorders

Area of Science:

• Hematology
• Oncology
• Vascular Biology

Background:

• Limited information exists on bone marrow (BM) angiogenesis in chronic myeloproliferative disorders (CMPDs).
• CD34 and CD105 are reliable markers for endothelial cells in BM.
• Quantification of microvascular density (MVD) requires parameters beyond simple counting, including blood flow characteristics.

Purpose of the Study:

• To investigate bone marrow angiogenesis in CMPDs.
• To compare vascularity in normal BM versus CMPDs.
• To evaluate the impact of therapeutic regimens on BM angiogenesis.

Main Methods:

• Immunohistochemical staining using CD34 and CD105.
• Quantification of microvascular density (MVD) using the hot spot method.
• Inclusion of parameters like microvessel area, shape, tortuosity, and branching.
• Three-dimensional reconstruction for architectural analysis.

Main Results:

• CMPDs, particularly chronic myeloid leukemia (CML), show increased MVD associated with elevated angiogenic cytokines and altered vessel structure (tortuosity, irregularity).
• Interferon therapy did not reduce vessel number, unlike Imatinib.
• Bone marrow transplantation initially increased MVD, normalizing after six months.
• Chronic idiopathic myelofibrosis shows increased MVD in advanced stages, with enhanced luminal distension and tortuosity.
• Essential thrombocythemia and polycythemia vera exhibit milder MVD increases with specific vascular characteristics.

Conclusions:

• Elaborate morphometrical methods are necessary for accurate assessment of BM vascular architecture in CMPDs.
• Angiogenesis in CMPDs is linked to myelofibrosis progression and can be influenced by therapies.
• BM microvascular anomalies in CMPDs may represent a target for anti-angiogenic therapies.