Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine

T. Menzel, Z. Rahman, E. Calleja, Kenneth White, E. L. Wilson, R. Wieder, J. Gabrilove

Research output: Contribution to journalArticle

154 Citations (Scopus)

Abstract

Chronic lymphocytic leukemia (CLL) is characterized by delayed senescence and slow accumulation of monoclonal, small lymphocytes. Basic fibroblast growth factor (bFGF) is a pleiotropic cytokine that plays a role in hematopoiesis and apoptosis. Elevated bFGF levels have been detected in urine from patients with a variety of neoplastic diseases including various leukemias; however, the cellular source of the bFGF has not been determined. In this study, the intracellular bFGF level in lymphocytes of 36 patients with B-CLL and 15 normal donors was determined using an enzyme-linked immunoassay. In cells derived from patients with high-risk disease, the median level of intracellular bFGF was 381.5 pg/2 x 105 cells, compared with a median of 90.5 pg/2 x 105 cells in patients with intermediate disease. In patients with low-risk disease, the median bFGF level was 4.9 pg/2 x 105 cells, and in normal controls, it was 6.0 pg/2 x 105 cells. The difference in the bFGF levels was significant for the comparison between low- and intermediate-risk (P = .00119), low- and high-risk (P < .0001), and intermediate- and high-risk disease (P = .0001). Immunofluorescent stains of peripheral blood mononuclear cells confirmed CLL lymphocytes as a cellular source of bFGF. To evaluate the potential contribution of elevated intracellular bFGF levels to the phenotype of CLL cells, leukemic cells were cultured in vitro with an apoptotic stimulus (fludarabine). CLL cells with high intracellular levels of bFGF appeared to be more resistant to fludarabine treatment. The addition of bFGF to fludarabine-treated CLL cells resulted in a delay of apoptosis and prolonged survival. These data suggest that bFGF may contribute to the resistance of CLL cells to an apoptotic stimulus.

Original languageEnglish (US)
Pages (from-to)1056-1063
Number of pages8
JournalBlood
Volume87
Issue number3
StatePublished - Feb 1 1996
Externally publishedYes

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Fibroblast Growth Factor 2
B-Cell Chronic Lymphocytic Leukemia
Lymphocytes
fludarabine
Apoptosis
Hematopoiesis
Immunoenzyme Techniques
Cultured Cells
Blood Cells
Leukemia
Blood
Coloring Agents
Tissue Donors
Urine
Cytokines
Phenotype

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine. / Menzel, T.; Rahman, Z.; Calleja, E.; White, Kenneth; Wilson, E. L.; Wieder, R.; Gabrilove, J.

In: Blood, Vol. 87, No. 3, 01.02.1996, p. 1056-1063.

Research output: Contribution to journalArticle

Menzel, T. ; Rahman, Z. ; Calleja, E. ; White, Kenneth ; Wilson, E. L. ; Wieder, R. ; Gabrilove, J. / Elevated intracellular level of basic fibroblast growth factor correlates with stage of chronic lymphocytic leukemia and is associated with resistance to fludarabine. In: Blood. 1996 ; Vol. 87, No. 3. pp. 1056-1063.
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abstract = "Chronic lymphocytic leukemia (CLL) is characterized by delayed senescence and slow accumulation of monoclonal, small lymphocytes. Basic fibroblast growth factor (bFGF) is a pleiotropic cytokine that plays a role in hematopoiesis and apoptosis. Elevated bFGF levels have been detected in urine from patients with a variety of neoplastic diseases including various leukemias; however, the cellular source of the bFGF has not been determined. In this study, the intracellular bFGF level in lymphocytes of 36 patients with B-CLL and 15 normal donors was determined using an enzyme-linked immunoassay. In cells derived from patients with high-risk disease, the median level of intracellular bFGF was 381.5 pg/2 x 105 cells, compared with a median of 90.5 pg/2 x 105 cells in patients with intermediate disease. In patients with low-risk disease, the median bFGF level was 4.9 pg/2 x 105 cells, and in normal controls, it was 6.0 pg/2 x 105 cells. The difference in the bFGF levels was significant for the comparison between low- and intermediate-risk (P = .00119), low- and high-risk (P < .0001), and intermediate- and high-risk disease (P = .0001). Immunofluorescent stains of peripheral blood mononuclear cells confirmed CLL lymphocytes as a cellular source of bFGF. To evaluate the potential contribution of elevated intracellular bFGF levels to the phenotype of CLL cells, leukemic cells were cultured in vitro with an apoptotic stimulus (fludarabine). CLL cells with high intracellular levels of bFGF appeared to be more resistant to fludarabine treatment. The addition of bFGF to fludarabine-treated CLL cells resulted in a delay of apoptosis and prolonged survival. These data suggest that bFGF may contribute to the resistance of CLL cells to an apoptotic stimulus.",
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