Bone Marrow in Polycythemia Vera, Chronic Myelocytic Leukemia, and Myelofibrosis Has an Increased Vascularity

Lundberg, Lena; Lerner, R.; Sundelin, P.; Rogers, Rick A.; Folkman, Judah; Palmblad, Jan

doi:10.1016/s0002-9440(10)64511-7

Cited by 201 publications

(169 citation statements)

References 8 publications

(6 reference statements)

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“…There is evidence that, similar to other hematopoietic disorders, 5,6 angiogenesis is involved in the pathogenesis and progression of CIMF. Serum levels of the proangiogenic cytokine VEGF and microvessel density (MVD) in the bone marrow are significantly increased in CIMF patients.…”

mentioning

confidence: 94%

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

et al. 2004

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Microvascular density (MVD) is substantially increased in bone marrow biopsies of patients with chronic idiopathic myelofibrosis (CIMF). CD105, a useful molecule for assessing MVD in various malignancies, is preferentially expressed by recently formed microvessels. Increased serum-soluble CD105 in patients with chronic myeloproliferative disorders, including CIMF, was documented. CD105 MVD has not so far been investigated in CIMF: to this end, the results in 55 patients with CIMF and 21 controls were compared with the conventional CD34 immunostaining as well as traditional histological and clinical disease features. The MVD mean values estimated by both CD105 and CD34 were significantly higher in CIMF patients than in controls (Po0.00001). In addition, the proportion of CD105-positive megakaryocytes was significantly higher in CIMF than in controls (Po0.0001). A degree of reticulin fibrosis 42 correlated with increased CD105 MVD (P ¼ 0.05). A multivariate analysis confirmed that CD105-positive MVD was an independent adverse prognosticator. This study demonstrates that while MVD, as assessed by both CD34 and CD105 immunostaining, is significantly increased in CIMF, only CD105-determined MVD correlates with the degree of fibrosis and is prognostically relevant. These findings provide a rationale for the investigational use of anti-CD105-targeted drugs in CIMF.

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mentioning

confidence: 94%

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

et al. 2004

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“…Microvessel number and branch points determined by confocal microscopy in studies also demonstrate increased branching from straight blood vessels in CML patients [7]. Studies on CML patients also show that BM angiogenesis plays an important role in the pathophysiology and prognosis of the disease.…”

Section: Why Hot Spots?mentioning

confidence: 81%

“…Haematological malignancies, have traditionally been regarded as "liquid tumours" because of the terminology and reflection of the disease process in the peripheral blood. Now there is evidence for the concept that these hematological malignancies may depend on vascular supply in the bone marrow like solid tumours in other tissues [7]. The data from studies also suggested that vascularity and angiogenic factors are increased in leukemias and MDS and may play a major role in the leukemogenic process.…”

Section: Introductionmentioning

confidence: 99%

Does CD34 Staining Reflect the Angiogenic Process in the Bone Marrow? An Analysis of a Series of Chronic Myeloid Leukemia Patients

Mahadevan

Basu

Kumar

2014

JCDR

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Backgorund: Angiogenesis is associated with growth, dissemin ation and metastasis of tumours. Measurement of Microvascular Density (MVD) is a quantitative method of assessment of angio genesis and would give a proportional co relate of the angiogenic process in tumours. The aim of this study is to measure the MVD by using CD34 staining in various phases of Chronic Myeloid Leukemia (CML) and type of CML (Granulocytic/Granulocytic Megakaryocytic) (G/GM) and to co relate micro vascular densities with the grade of fibrosis. Materials and Methods:Bone marrow biopsy specimens of 30 CML patients and 20 non CML (controls) cases that required bone marrow biopsy were subjected to CD34 staining and H&E staining. The mean MVD in CD34 slides was assessed by selecting hot spots and MVD was measured in these fields in high power (40 x magnification) and the mean MVD was calculated by taking the average of four hot spots per field. Grade of fibrosis and phase of CML, type (G/GM) were assessed in H&E slides. The controls were matched with respect to age and gender.Results: Among 30 patients with CML, 21 were in chronic phase, five in accelerated and four in blast crisis. A normal distribution was obtained for MVD of both CML cases and controls using tests for normality. Comparison of mean MVD between CML and controls by student t test showed a significant increase in MVD of CML cases (p = 0.00026). However, no significant difference in MVD between the three phases viz, Chronic, accelerated and blast crisis phase (p = 0.302) was obtained by using one way ANOVA. Comparison of Grade of fibrosis with MVD using independent t test showed no significant difference in MVD between low (Grade1&2) and high grade (Grade 3&4) (p = 0.805). No significant difference in MVD was obtained between G and GM types of CML using independent t test (p =0.381). Conclusion:The study shows that there is a significant increase in MVD in CML cases than controls but no significant difference in MVD could be demonstrated between different phases of CML, histological types of CML and grades of fibrosis in CML.

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“…Bone marrow biopsies from seven patients with CML, seven patients with PV and from five healthy subjects were obtained for routine diagnostic procedures and retrieved as previously described (Lundberg et al, 2000). The control group consisted of patients who had been investigated because of diagnosis of either anaemia or leukocytosis, but who had a normal bone marrow according to routine examination by a specialized haemopathologist.…”

Section: Methodsmentioning

confidence: 99%

“…These features are particularly evident in chronic myeloid leukaemia (CML) and myelofibrosis, whereas polycythaemia vera (PV) marrows may not display significantly increased vascularity, but show abnormal vascular architecture (Lundberg et al, 2000).…”

mentioning

confidence: 99%

Expression of cox‐2, tie‐2 and glycodelin by megakaryocytes in patients with chronic myeloid leukaemia and polycythaemia vera

Zetterberg¹,

Lundberg

Palmblad³

2003

Br J Haematol

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Summary. When evaluating bone marrow sections for markers of neo-angiogenesis, we found that megakaryocytes stained markedly positive for cyclooxygenase-2 (Cox-2), Tie-2 and glycodelin. This apparently novel finding was further evaluated for disease-specific variations. Bone marrow sections from two patient groups, known to be characterized by clonal megakaryocytopoiesis, viz. chronic myeloid leukaemia and polycythaemia vera, stained, however, similarly to healthy marrows for these markers. The biochemical background and clinical significance of Cox-2, Tie-2 and glycodelin remains to be elucidated.

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Bone Marrow in Polycythemia Vera, Chronic Myelocytic Leukemia, and Myelofibrosis Has an Increased Vascularity

Cited by 201 publications

References 8 publications

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

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

Does CD34 Staining Reflect the Angiogenic Process in the Bone Marrow? An Analysis of a Series of Chronic Myeloid Leukemia Patients

Expression of cox‐2, tie‐2 and glycodelin by megakaryocytes in patients with chronic myeloid leukaemia and polycythaemia vera

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