Elevated serum B-lymphocyte stimulator levels in patients with familial lymphoproliferative disorders

Anne J Novak, Deanna M. Grote, Steven C. Ziesmer, Michael P. Kline, Michelle K. Manske, Susan L Slager, Thomas Elmer Witzig, Tait Shanafelt, Timothy G. Call, Neil Elliot Kay, Diane F Jelinek, James R Cerhan, Jane A. Gross, Brandon Harder, Stacey R. Dillon, Stephen Maxted Ansell

Research output: Contribution to journalArticle

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Abstract

Purpose: Serum B-lymphocyte stimulator (BLyS) levels have been found to be elevated in a number of immune disease models. Therefore, we sought to establish whether BLyS levels were elevated in patients with B-cell lymphoproliferative disorders and to determine whether elevated BLyS levels correlated with clinical characteristics of the disease. Patients and Methods: Specimens were collected from the peripheral blood of individuals diagnosed with B-cell chronic lymphocytic leukemia (B-CLL; n = 70) or from age- and sex-matched patients seen at the same institution (n = 41). Serum BLyS levels were determined by enzyme-linked immunosorbent assay, and sequencing of the BLyS promoter was performed by conventional methods and confirmed by restriction fragment length polymorphism analysis. Results: We found that elevated BLyS levels were more common in patients with familial B-CLL than individuals with sporadic B-CLL or normal controls. Because of this association, we sequenced the BLyS promoter in patients with B-CLL and normal controls and identified a polymorphic site, -871 C/T. We found that the wild-type sequence was significantly underrepresented in patients with familial B-CLL (4%) compared with patients with sporadic B-CLL (30%; P = .01) or controls (24%; P = .04). Furthermore, using a luciferase reporter under control of the BLyS promoter containing either a C or a T at position -871, we found that the reporter construct containing a T at -871 had a 2.6-fold increase in activity (P = .004). Conclusion: Our data suggest serum BLyS levels are elevated in patients with familial B-CLL and that elevated BLyS levels correlate with the presence of a T at -871 in the BLyS promoter.

Original languageEnglish (US)
Pages (from-to)983-987
Number of pages5
JournalJournal of Clinical Oncology
Volume24
Issue number6
DOIs
StatePublished - Feb 20 2006

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B-Cell Activating Factor
Lymphoproliferative Disorders
Serum
Immune System Diseases
B-Cell Chronic Lymphocytic Leukemia
Luciferases
Restriction Fragment Length Polymorphisms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Elevated serum B-lymphocyte stimulator levels in patients with familial lymphoproliferative disorders. / Novak, Anne J; Grote, Deanna M.; Ziesmer, Steven C.; Kline, Michael P.; Manske, Michelle K.; Slager, Susan L; Witzig, Thomas Elmer; Shanafelt, Tait; Call, Timothy G.; Kay, Neil Elliot; Jelinek, Diane F; Cerhan, James R; Gross, Jane A.; Harder, Brandon; Dillon, Stacey R.; Ansell, Stephen Maxted.

In: Journal of Clinical Oncology, Vol. 24, No. 6, 20.02.2006, p. 983-987.

Research output: Contribution to journalArticle

Novak, Anne J ; Grote, Deanna M. ; Ziesmer, Steven C. ; Kline, Michael P. ; Manske, Michelle K. ; Slager, Susan L ; Witzig, Thomas Elmer ; Shanafelt, Tait ; Call, Timothy G. ; Kay, Neil Elliot ; Jelinek, Diane F ; Cerhan, James R ; Gross, Jane A. ; Harder, Brandon ; Dillon, Stacey R. ; Ansell, Stephen Maxted. / Elevated serum B-lymphocyte stimulator levels in patients with familial lymphoproliferative disorders. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 6. pp. 983-987.
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abstract = "Purpose: Serum B-lymphocyte stimulator (BLyS) levels have been found to be elevated in a number of immune disease models. Therefore, we sought to establish whether BLyS levels were elevated in patients with B-cell lymphoproliferative disorders and to determine whether elevated BLyS levels correlated with clinical characteristics of the disease. Patients and Methods: Specimens were collected from the peripheral blood of individuals diagnosed with B-cell chronic lymphocytic leukemia (B-CLL; n = 70) or from age- and sex-matched patients seen at the same institution (n = 41). Serum BLyS levels were determined by enzyme-linked immunosorbent assay, and sequencing of the BLyS promoter was performed by conventional methods and confirmed by restriction fragment length polymorphism analysis. Results: We found that elevated BLyS levels were more common in patients with familial B-CLL than individuals with sporadic B-CLL or normal controls. Because of this association, we sequenced the BLyS promoter in patients with B-CLL and normal controls and identified a polymorphic site, -871 C/T. We found that the wild-type sequence was significantly underrepresented in patients with familial B-CLL (4{\%}) compared with patients with sporadic B-CLL (30{\%}; P = .01) or controls (24{\%}; P = .04). Furthermore, using a luciferase reporter under control of the BLyS promoter containing either a C or a T at position -871, we found that the reporter construct containing a T at -871 had a 2.6-fold increase in activity (P = .004). Conclusion: Our data suggest serum BLyS levels are elevated in patients with familial B-CLL and that elevated BLyS levels correlate with the presence of a T at -871 in the BLyS promoter.",
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T1 - Elevated serum B-lymphocyte stimulator levels in patients with familial lymphoproliferative disorders

AU - Novak, Anne J

AU - Grote, Deanna M.

AU - Ziesmer, Steven C.

AU - Kline, Michael P.

AU - Manske, Michelle K.

AU - Slager, Susan L

AU - Witzig, Thomas Elmer

AU - Shanafelt, Tait

AU - Call, Timothy G.

AU - Kay, Neil Elliot

AU - Jelinek, Diane F

AU - Cerhan, James R

AU - Gross, Jane A.

AU - Harder, Brandon

AU - Dillon, Stacey R.

AU - Ansell, Stephen Maxted

PY - 2006/2/20

Y1 - 2006/2/20

N2 - Purpose: Serum B-lymphocyte stimulator (BLyS) levels have been found to be elevated in a number of immune disease models. Therefore, we sought to establish whether BLyS levels were elevated in patients with B-cell lymphoproliferative disorders and to determine whether elevated BLyS levels correlated with clinical characteristics of the disease. Patients and Methods: Specimens were collected from the peripheral blood of individuals diagnosed with B-cell chronic lymphocytic leukemia (B-CLL; n = 70) or from age- and sex-matched patients seen at the same institution (n = 41). Serum BLyS levels were determined by enzyme-linked immunosorbent assay, and sequencing of the BLyS promoter was performed by conventional methods and confirmed by restriction fragment length polymorphism analysis. Results: We found that elevated BLyS levels were more common in patients with familial B-CLL than individuals with sporadic B-CLL or normal controls. Because of this association, we sequenced the BLyS promoter in patients with B-CLL and normal controls and identified a polymorphic site, -871 C/T. We found that the wild-type sequence was significantly underrepresented in patients with familial B-CLL (4%) compared with patients with sporadic B-CLL (30%; P = .01) or controls (24%; P = .04). Furthermore, using a luciferase reporter under control of the BLyS promoter containing either a C or a T at position -871, we found that the reporter construct containing a T at -871 had a 2.6-fold increase in activity (P = .004). Conclusion: Our data suggest serum BLyS levels are elevated in patients with familial B-CLL and that elevated BLyS levels correlate with the presence of a T at -871 in the BLyS promoter.

AB - Purpose: Serum B-lymphocyte stimulator (BLyS) levels have been found to be elevated in a number of immune disease models. Therefore, we sought to establish whether BLyS levels were elevated in patients with B-cell lymphoproliferative disorders and to determine whether elevated BLyS levels correlated with clinical characteristics of the disease. Patients and Methods: Specimens were collected from the peripheral blood of individuals diagnosed with B-cell chronic lymphocytic leukemia (B-CLL; n = 70) or from age- and sex-matched patients seen at the same institution (n = 41). Serum BLyS levels were determined by enzyme-linked immunosorbent assay, and sequencing of the BLyS promoter was performed by conventional methods and confirmed by restriction fragment length polymorphism analysis. Results: We found that elevated BLyS levels were more common in patients with familial B-CLL than individuals with sporadic B-CLL or normal controls. Because of this association, we sequenced the BLyS promoter in patients with B-CLL and normal controls and identified a polymorphic site, -871 C/T. We found that the wild-type sequence was significantly underrepresented in patients with familial B-CLL (4%) compared with patients with sporadic B-CLL (30%; P = .01) or controls (24%; P = .04). Furthermore, using a luciferase reporter under control of the BLyS promoter containing either a C or a T at position -871, we found that the reporter construct containing a T at -871 had a 2.6-fold increase in activity (P = .004). Conclusion: Our data suggest serum BLyS levels are elevated in patients with familial B-CLL and that elevated BLyS levels correlate with the presence of a T at -871 in the BLyS promoter.

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