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Dysregulated angiogenesis in B-chronic lymphocytic leukemia: morphologic, immunohistochemical, and flow cytometric evidence.

Publication ,  Journal Article
Frater, JL; Kay, NE; Goolsby, CL; Crawford, SE; Dewald, GW; Peterson, LC
Published in: Diagn Pathol
April 18, 2008

BACKGROUND: The extent of enhanced bone marrow angiogenesis in chronic lymphocytic leukemia (CLL) and relationship to proangiogenic factors and prognostic indicators is largely unexplored. METHODS: To further investigate the role of angiogenesis in CLL by evaluating the topography and extent of angiogenesis in a group of CLL bone marrow biopsies, to study the expression of pro and antiangiogenic vascular factors in CLL cells to more precisely document the cell types producing these factors, and to evaluate the role, if any, of localized hypoxia in upregulation of angiogenesis in CLL We used immunohistochemistry (IHC) (n = 21 pts) with antibodies to CD3 and CD20, proangiogenic (VEGF, HIF-1a) and antiangiogenic (TSP-1) factors, and VEGF receptors -1 and -2 to examine pattern/extent of CLL marrow involvement, microvessel density (MVD), and angiogenic characteristics; flow cytometry (FC) was performed on 21 additional cases for VEGF and TSP-1. RESULTS: CLL patients had higher MVD (23.8 vs 14.6, p~0.0002) compared to controls (n = 10). MVD was highest at the periphery of focal infiltrates, was not enhanced in proliferation centers, and was increased irrespective of the presence or absence of cytogenetic/immunophenotypic markers of aggressivity. By IHC, CLL cells were VEGF(+), HIF-1a (+), TSP-1(-), VEGFR-1(+), and VEGFR-2(+). By FC, CLL cells were 1.4-2.0-fold brighter for VEGF than T cells and were TSP-1(-). CONCLUSION: CLL demonstrates enhanced angiogenesis, with increased MVD, upregulated VEGF and downregulated TSP-1. Upregulation of HIF-1a in all CLL cases suggests localized tissue hypoxia as an important stimulant of microvessel proliferation. The presence of VEGF receptors on CLL cells implies an autocrine effect for VEGF. Differences in MVD did not correlate with traditional genetic/immunophenotypic markers of aggressiveness.

Duke Scholars

Published In

Diagn Pathol

DOI

EISSN

1746-1596

Publication Date

April 18, 2008

Volume

3

Start / End Page

16

Location

England

Related Subject Headings

  • Pathology
  • 3202 Clinical sciences
 

Citation

APA
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MLA
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Frater, J. L., Kay, N. E., Goolsby, C. L., Crawford, S. E., Dewald, G. W., & Peterson, L. C. (2008). Dysregulated angiogenesis in B-chronic lymphocytic leukemia: morphologic, immunohistochemical, and flow cytometric evidence. Diagn Pathol, 3, 16. https://doi.org/10.1186/1746-1596-3-16
Frater, John L., Neil E. Kay, Charles L. Goolsby, Susan E. Crawford, Gordon W. Dewald, and LoAnn C. Peterson. “Dysregulated angiogenesis in B-chronic lymphocytic leukemia: morphologic, immunohistochemical, and flow cytometric evidence.Diagn Pathol 3 (April 18, 2008): 16. https://doi.org/10.1186/1746-1596-3-16.
Frater JL, Kay NE, Goolsby CL, Crawford SE, Dewald GW, Peterson LC. Dysregulated angiogenesis in B-chronic lymphocytic leukemia: morphologic, immunohistochemical, and flow cytometric evidence. Diagn Pathol. 2008 Apr 18;3:16.
Frater, John L., et al. “Dysregulated angiogenesis in B-chronic lymphocytic leukemia: morphologic, immunohistochemical, and flow cytometric evidence.Diagn Pathol, vol. 3, Apr. 2008, p. 16. Pubmed, doi:10.1186/1746-1596-3-16.
Frater JL, Kay NE, Goolsby CL, Crawford SE, Dewald GW, Peterson LC. Dysregulated angiogenesis in B-chronic lymphocytic leukemia: morphologic, immunohistochemical, and flow cytometric evidence. Diagn Pathol. 2008 Apr 18;3:16.
Journal cover image

Published In

Diagn Pathol

DOI

EISSN

1746-1596

Publication Date

April 18, 2008

Volume

3

Start / End Page

16

Location

England

Related Subject Headings

  • Pathology
  • 3202 Clinical sciences