Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia by Teresa Padró, Sandra Ruiz, Ralf Bieker, Horst Bürger, Martin Steins,

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Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia by Teresa Padró, Sandra Ruiz, Ralf Bieker, Horst Bürger, Martin Steins, Joachim Kienast, Thomas Büchner, Wolfgang E. Berdel, and Rolf M. Mesters Blood Volume 95(8):2637-2644 April 15, 2000 ©2000 by American Society of Hematology

Immunohistochemical staining of bone marrow sections from patients with acute myeloid leukemia (AML) at presentation (A and C) and control patients (B and D) using antibodies against thrombomodulin (TM) (A and B) and von Willebrand factor (vWF) (C and D).No... Immunohistochemical staining of bone marrow sections from patients with acute myeloid leukemia (AML) at presentation (A and C) and control patients (B and D) using antibodies against thrombomodulin (TM) (A and B) and von Willebrand factor (vWF) (C and D).Note that endothelial cell sprouts and small microvessels without visible lumina were prevailing in AML sections (red staining in A and C), contrasting with big and well-shaped vessels in the controls (B and D). Original magnification ×500. Teresa Padró et al. Blood 2000;95:2637-2644 ©2000 by American Society of Hematology

Microvessel density in the bone marrow from 62 patients with acute myeloid leukemia (AML) at presentation and from 22 control patients.Microvessel quantification was performed in adjacent sections of each bone marrow biopsy stained in parallel for thrombomo... Microvessel density in the bone marrow from 62 patients with acute myeloid leukemia (AML) at presentation and from 22 control patients.Microvessel quantification was performed in adjacent sections of each bone marrow biopsy stained in parallel for thrombomodulin (TM) (A) and von Willebrand factor (vWF) (B) as described in “Materials and methods.” Data are presented as individual values (open circles) and interquartile ranges (boxes). The difference in microvessel counts between the 2 groups was statistically significant (P < .0001 for TM as well as for vWF; Mann-Whitney rank sum test for independent groups). Teresa Padró et al. Blood 2000;95:2637-2644 ©2000 by American Society of Hematology

Microvessel counts of the bone marrow from 20 patients with acute myeloid leukemia (AML) and from 10 control patients expressed as the sum of microvessels in an area of 1.50 mm2[thrombomodulin (TM) staining].The difference between groups was statistically s... Microvessel counts of the bone marrow from 20 patients with acute myeloid leukemia (AML) and from 10 control patients expressed as the sum of microvessels in an area of 1.50 mm2[thrombomodulin (TM) staining].The difference between groups was statistically significant (P = .0001; Mann-Whitney rank sum test for independent groups). The insert denotes the regression line (r = 0.960,P < .0001) for microvessel counts obtained using hot spots (mean value of three 0.125 mm2 fields) and using a larger area of 1.5 mm2 from the same bone marrow sections. Teresa Padró et al. Blood 2000;95:2637-2644 ©2000 by American Society of Hematology

Relationship between microvessel counts per ×500 field in adjacent sections of the bone marrow stained for thrombomodulin (TM) or von Willebrand factor (vWF).For each sample (62 patients with acute myeloid leukemia [AML] and 22 control patients), microvesse... Relationship between microvessel counts per ×500 field in adjacent sections of the bone marrow stained for thrombomodulin (TM) or von Willebrand factor (vWF).For each sample (62 patients with acute myeloid leukemia [AML] and 22 control patients), microvessel density measured by vWF staining was plotted against the microvessel density obtained with TM staining. Significance of the regression analysis was calculated by the Pearson test (r = 0.875, P < .0001). Teresa Padró et al. Blood 2000;95:2637-2644 ©2000 by American Society of Hematology

Effects of induction chemotherapy on microvessel density in the bone marrow of patients with acute myeloid leukemia (AML).Microvessel counts are depicted for day 0 (presentation), day 16 of induction chemotherapy, the time of complete remission, and the con... Effects of induction chemotherapy on microvessel density in the bone marrow of patients with acute myeloid leukemia (AML).Microvessel counts are depicted for day 0 (presentation), day 16 of induction chemotherapy, the time of complete remission, and the control patients. Values are given as individual data points (mean values of microvessel counts for thrombomodulin [TM] and von Willebrand factor [vWF] staining). The difference of microvessel density for day 16 and complete remission was statistically significant compared with day 0 (P < .0001; Mann-Whitney test). On day 16, patients with at least 5% residual blast infiltration (closed circles) had higher microvessel counts than patients without blast infiltration (open circles; P < .001, Mann-Whitney test). Teresa Padró et al. Blood 2000;95:2637-2644 ©2000 by American Society of Hematology

Immunohistochemical staining of marrows with anti-thrombomodulin (TM) antibodies on day 16 of induction chemotherapy.(A) Section from a bone marrow without residual blast infiltration. Immunohistochemical staining of marrows with anti-thrombomodulin (TM) antibodies on day 16 of induction chemotherapy.(A) Section from a bone marrow without residual blast infiltration. (B) Section from a bone marrow with 10% residual leukemic blast infiltration. Note the bigger size and sinusoidal appearance of the microvessels compared with those on day 0 (Figure 1A and 1C). Original magnification ×500. Teresa Padró et al. Blood 2000;95:2637-2644 ©2000 by American Society of Hematology

Microvessel density on day 0 compared with day 16 and day 16 compared with complete remission.(A) Microvessel density on day 16 (d 16) of induction chemotherapy compared with presentation (d 0). Microvessel density on day 0 compared with day 16 and day 16 compared with complete remission.(A) Microvessel density on day 16 (d 16) of induction chemotherapy compared with presentation (d 0). (B) Pair comparisons of microvessel density between day 16 (d 16) of induction chemotherapy and the time of complete remission (CR). In (A) “blast –” refers to patients without residual leukemic blast infiltration and “blast +” to patients with at least 5% residual leukemic blast infiltration. In A and B, each pair of dots linked by a line represents the values from an individual patient. The difference in microvessel counts between day 0 and day 16 in the “blast –” group was statistically significant (P < .001, Wilcoxon test), in contrast to the “blast +” group (P = .052). No differences were found by Wilcoxon test (P = .185) between day 16 and the time of complete remission. Teresa Padró et al. Blood 2000;95:2637-2644 ©2000 by American Society of Hematology