Angiogenesis in CLL

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As a new member here without access as yet to the prior messages, this may

be redundant. However, I have wondered about the dynamics of B

CLL cell production and the steady increase of this capability in the bone

marrow seems to be a likely candidate for a source.

This URL has been posted on the CLL list.

http://www.bloodjournal.org/cgi/content/full/97/8/2529 ....

Blood, 15 April 2001, Vol. 97, No. 8, pp. 2529-2530

Angiogenesis is increased in B-cell chronic lymphocytic leukemia

Aguayo and colleagues recently reported elevated levels of vascular

endothelial growth factor (VEGF) in the cells of B-cell chronic lymphocytic

leukemia (CLL).1 When discussing the possible significance of the elevated

VEGF levels in CLL, the authors cite their prior abstract in which they

report no significant increase in vascularity in bone marrow biopsies from

patients with CLL.2

The relationship of VEGF and other growth factors to bone marrow

angiogenesis is important in determining their possible role in the

pathogenesis of CLL. Therefore, we wish to make the readers aware of our

study that reports significantly increased angiogenesis in bone marrow

biopsies from patients with CLL.3

In our study, we quantified the degree of angiogenesis in CLL by measuring

microvessel density in bone marrow biopsy trephine sections from controls

and CLL patients using a method previously described.4 The control marrows

were of comparable age and were negative for any infiltrating lesions. The

microvessels in the bone marrow sections were delineated by

immunohistochemistry using antibodies to CD34. The bone marrow sections from

the CLL patients (Figure 1) had a mean microvessel density of 7.64 per high

power field (hpf), in contrast to the control samples (Figure 2), which had

a mean microvessel density of 2.11/hpf (P = .0001). The mean hot-spot

microvessel density, the area with the highest microvessel density, was also

significantly higher in CLL than in the control biopsy sections (P = .0008).

Importantly, we also noted significant elevations of another vascular growth

factor, bFGF, in the urine of CLL patients compared to controls. Thus based

on the recent paper by Aguayo and our own work, there is evidence for

increased or abnormal levels of 2 vascular growth factors in CLL.

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Figure 1. Increased vascularity in CLL bone

marrow. Bone marrow trephine biopsy from CLL patient with several

microvessels (arrows) highlighted by immunohistochemistry using antibodies

to CD34.

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Figure 2. Vascularity in control bone marrow.

Bone marrow biopsy from control with one microvessel (arrow) highlighted by

immunohistochemistry using antibodies to CD34.

The paper by Aguayo is important because it contributes to our knowledge

about the possible factors that might be important in the growth and

proliferation of the B-cells in CLL. Correlation of angiogenesis in bone

marrow trephine biopsies and other tissues typically involved in CLL,5 such

as lymph nodes with the levels and functions of other growth factors and

cytokines, is critical in further defining the nature of these

relationships. We believe that our findings add to the evidence that

angiogenic factors are dysregulated in CLL and that one endpoint of this may

be the abnormal angiogenesis found in CLL marrows.

LoAnn and Ameet R. Kini

Department of Pathology Northwestern University Medical School Chicago, IL

Neil Kay

Department of Medicine Section of Hematology/Oncology Mayo Clinic Medical

School Rochester, MN

References

1. Aguayo A, O'Brien S, Keating M, et al. Clinical relevance of

intracellular vascular endothelial growth factor levels in B-cell chronic

lymphocytic leukemia. Blood. 2000;96:768-770[Abstract/Full Text].

2. Aguayo A, Kantarjian H, Talpaz M, et al. Increased angiogenesis in

chronic myeloid leukemia and myelodysplastic syndromes [abstract]. Blood.

1998;92:607a.

3. Kini AR, Kay NE, LC. Increased bone marrow angiogenesis in

B-cell chronic lymphocytic leukemia. Leukemia. 2000;14:1414-1418[Medline].

4. Weidner N, Semple J, Welch W, et al. Tumor angiogenesis and

metastasis-correlation in invasive breast carcinoma. N Engl J Med.

1991;324:1-8[Medline].

5. Chen H, Treweeke AT, West DC, et al. In vitro and in vivo production of

vascular endothelial growth factor by chronic lymphocytic leukemia cells.

Blood. 2000;96:3181-3187[Abstract/Full Text].