Clinical relevance of intracellular vascular endothelial growth factor levels in B-cell chronic lymphocytic leukemia.

Strong evidence exists for an association between high vascular endothelial growth factor (VEGF) levels and poor prognoses in patients with solid tumors and acute leukemia. Using Western blot analysis and solid-phase radioimmunoassay, we measured cellular VEGF levels in B-cell chronic lymphocytic leukemia (CLL) samples from 225 patients and correlated these levels with disease characteristics and prognoses. The median VEGF level in CLL samples was 7.26 times the median level detected in normal peripheral blood mononuclear cells. Patients with lower levels of VEGF protein showed a trend toward shorter survival (P =.07). However, in a subgroup of CLL patients with good prognoses or early-stage disease (Rai stages 0-II, Binet stages A,B; beta2-M </= 2.8 mg/dL), lower levels of VEGF were associated with shorter survival times. For the entire group of patients, no correlation was found between VEGF levels and beta2-M levels or Rai and Binet stage. Most samples from patients with CLL expressed the 43-kd VEGF isoform in addition to the commonly expressed 45-kd isoform. It remains to be seen whether the expression of the 43-kd isoform is responsible for this reversed correlation with outcome. (Blood. 2000;96:768-770)

[1]  E. Estey,et al.  Cellular vascular endothelial growth factor is a predictor of outcome in patients with acute myeloid leukemia. , 1999, Blood.

[2]  T. Grogan,et al.  Expression of vascular endothelial growth factor and its receptors in hematopoietic malignancies. , 1999, Cancer research.

[3]  H. Kantarjian,et al.  Deficiency of the ATM protein expression defines an aggressive subgroup of B-cell chronic lymphocytic leukemia. , 1998, Cancer research.

[4]  H. Joensuu,et al.  High pre‐treatment serum level of vascular endothelial growth factor (VEGF) is associated with poor outcome in small‐cell lung cancer , 1998, International journal of cancer.

[5]  L. Ellis,et al.  Vessel counts and vascular endothelial growth factor expression in pancreatic adenocarcinoma. , 1998, European journal of cancer.

[6]  H. Joensuu,et al.  A high pretreatment serum vascular endothelial growth factor concentration is associated with poor outcome in non-Hodgkin's lymphoma. , 1997, Blood.

[7]  S. Ergün,et al.  Vascular endothelial growth factor, a possible paracrine growth factor in human acute myeloid leukemia. , 1997, Blood.

[8]  S. Sallan,et al.  Spectrum of tumor angiogenesis in the bone marrow of children with acute lymphoblastic leukemia. , 1997, The American journal of pathology.

[9]  M. Toi,et al.  Clinical significance of the determination of angiogenic factors. , 1996, European journal of cancer.

[10]  M. Rocchi,et al.  Assignment of the vascular endothelial growth factor gene to human chromosome 6p21.3. , 1996, Circulation.

[11]  J. Folkman Clinical Applications of Research on Angiogenesis , 1995 .

[12]  L. Ellis,et al.  Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer. , 1995, Cancer research.

[13]  A. Harris,et al.  Different angiogenic pathways characterize superficial and invasive bladder cancer. , 1995, Cancer research.

[14]  M. Toi,et al.  Association of Vascular Endothelial Growth Factor Expression with Tumor Angiogenesis and with Early Relapse in Primary Breast Cancer , 1994, Japanese journal of cancer research : Gann.

[15]  J. Fiddes,et al.  The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. , 1991, The Journal of biological chemistry.

[16]  D. Goeddel,et al.  Vascular endothelial growth factor is a secreted angiogenic mitogen. , 1989, Science.

[17]  D. Gospodarowicz,et al.  Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT‐20 cells. , 1989, The EMBO journal.

[18]  N. Ferrara,et al.  Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. , 1989, Biochemical and biophysical research communications.

[19]  J. Folkman Angiogenesis in cancer, vascular, rheumatoid and other disease , 1995, Nature Medicine.

[20]  J. Folkman Seminars in Medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis. , 1995, The New England journal of medicine.

[21]  J. Winer,et al.  Binding sites for vascular endothelial growth factor are localized on endothelial cells in adult rat tissues. , 1992, The Journal of clinical investigation.