B-chronic lymphocytic leukemia cells contain both endogenous κ immunoglobulin mRNA and critical immunoglobulin gene activation transcription factors

Sara L. Zaknoen, Susan L. Christian, Rosa Suen, Brian Van Ness, Neil Elliot Kay

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

B-cell chronic lymphocytic leukemia (B-CLL) is a hematologic malignancy characterized by the proliferation and accumulation of mature-looking B lymphocytes. Patients with B-CLL exhibit a number of immune defects including: auto-antibodies, depressed cell-mediated immunity and hypogammaglobulinemia (HG). We investigated the control of Ig production in the malignant CLL 8-cell at a transcriptional and translation level. We isolated fresh leukemic B-cells from CLL patients and analyzed for the presence of nuclear factors OCT-1, OCT-2, and NF-KB. Malignant B-cells were purified to >90% B-cells, and total cellular RNA and nuclear proteins were isolated from these cells. Mobility shift assays were probed with 32P-labeled oligonucleotides specific to the immunoglobulin (Ig) enhancer and promotor regions. We detected endogenous OCT-1, OCT-2, and NF-KB in all patients tested (n = 5). We then evaluated whether activation of CLL B cells could augment κ-mRNA levels. CLL cells (n = 3) exposed to phorbol ester and A23187 were harvested at 0, 2, 4, 8, and 48 min and examined for κ-mRNA by Northern blot. All CLL patients (n = 3) had easily detectable levels of endogenous κ-mRNA. However, only one patient had an obvious increase in κ-mRNA post-induction with TPA/A23187. There was no concomitant increase in this patient's OCT-1, OCT-2, of NF-KB level. This finding prompted us to survey other B-CLL patients (n = 6) for Ig nuclear transcriptional factors pre- and post-induction. In summary, CLL B cells express Ig transcriptional factor OCT-1, OCT-2, and NF-KB constitutively. The endogenous level of NF-KB may account for the basal κ-mRNA detected in B-CLL cells. However, the inability to augment NF-KB levels may, in part, explain the low levels of Ig synthesis in CLL B-cells.

Original languageEnglish (US)
Pages (from-to)675-679
Number of pages5
JournalLeukemia
Volume6
Issue number7
StatePublished - Jul 1992
Externally publishedYes

Fingerprint

Immunoglobulin Genes
B-Cell Chronic Lymphocytic Leukemia
Transcriptional Activation
Immunoglobulins
B-Lymphocytes
Transcription Factors
Messenger RNA
Calcimycin
NFI Transcription Factors
Agammaglobulinemia
Electrophoretic Mobility Shift Assay
Phorbol Esters
Hematologic Neoplasms
Nuclear Proteins
Genetic Promoter Regions
Cellular Immunity
Oligonucleotides
Northern Blotting
RNA
Antibodies

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

B-chronic lymphocytic leukemia cells contain both endogenous κ immunoglobulin mRNA and critical immunoglobulin gene activation transcription factors. / Zaknoen, Sara L.; Christian, Susan L.; Suen, Rosa; Van Ness, Brian; Kay, Neil Elliot.

In: Leukemia, Vol. 6, No. 7, 07.1992, p. 675-679.

Research output: Contribution to journalArticle

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abstract = "B-cell chronic lymphocytic leukemia (B-CLL) is a hematologic malignancy characterized by the proliferation and accumulation of mature-looking B lymphocytes. Patients with B-CLL exhibit a number of immune defects including: auto-antibodies, depressed cell-mediated immunity and hypogammaglobulinemia (HG). We investigated the control of Ig production in the malignant CLL 8-cell at a transcriptional and translation level. We isolated fresh leukemic B-cells from CLL patients and analyzed for the presence of nuclear factors OCT-1, OCT-2, and NF-KB. Malignant B-cells were purified to >90{\%} B-cells, and total cellular RNA and nuclear proteins were isolated from these cells. Mobility shift assays were probed with 32P-labeled oligonucleotides specific to the immunoglobulin (Ig) enhancer and promotor regions. We detected endogenous OCT-1, OCT-2, and NF-KB in all patients tested (n = 5). We then evaluated whether activation of CLL B cells could augment κ-mRNA levels. CLL cells (n = 3) exposed to phorbol ester and A23187 were harvested at 0, 2, 4, 8, and 48 min and examined for κ-mRNA by Northern blot. All CLL patients (n = 3) had easily detectable levels of endogenous κ-mRNA. However, only one patient had an obvious increase in κ-mRNA post-induction with TPA/A23187. There was no concomitant increase in this patient's OCT-1, OCT-2, of NF-KB level. This finding prompted us to survey other B-CLL patients (n = 6) for Ig nuclear transcriptional factors pre- and post-induction. In summary, CLL B cells express Ig transcriptional factor OCT-1, OCT-2, and NF-KB constitutively. The endogenous level of NF-KB may account for the basal κ-mRNA detected in B-CLL cells. However, the inability to augment NF-KB levels may, in part, explain the low levels of Ig synthesis in CLL B-cells.",
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AB - B-cell chronic lymphocytic leukemia (B-CLL) is a hematologic malignancy characterized by the proliferation and accumulation of mature-looking B lymphocytes. Patients with B-CLL exhibit a number of immune defects including: auto-antibodies, depressed cell-mediated immunity and hypogammaglobulinemia (HG). We investigated the control of Ig production in the malignant CLL 8-cell at a transcriptional and translation level. We isolated fresh leukemic B-cells from CLL patients and analyzed for the presence of nuclear factors OCT-1, OCT-2, and NF-KB. Malignant B-cells were purified to >90% B-cells, and total cellular RNA and nuclear proteins were isolated from these cells. Mobility shift assays were probed with 32P-labeled oligonucleotides specific to the immunoglobulin (Ig) enhancer and promotor regions. We detected endogenous OCT-1, OCT-2, and NF-KB in all patients tested (n = 5). We then evaluated whether activation of CLL B cells could augment κ-mRNA levels. CLL cells (n = 3) exposed to phorbol ester and A23187 were harvested at 0, 2, 4, 8, and 48 min and examined for κ-mRNA by Northern blot. All CLL patients (n = 3) had easily detectable levels of endogenous κ-mRNA. However, only one patient had an obvious increase in κ-mRNA post-induction with TPA/A23187. There was no concomitant increase in this patient's OCT-1, OCT-2, of NF-KB level. This finding prompted us to survey other B-CLL patients (n = 6) for Ig nuclear transcriptional factors pre- and post-induction. In summary, CLL B cells express Ig transcriptional factor OCT-1, OCT-2, and NF-KB constitutively. The endogenous level of NF-KB may account for the basal κ-mRNA detected in B-CLL cells. However, the inability to augment NF-KB levels may, in part, explain the low levels of Ig synthesis in CLL B-cells.

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