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Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
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CCL3 as Possible Negative Prognostic Factor in Chronic Lymphocytic Leukemia.

Sylwia Popek-Marciniec1, Szymon Zmorzyński1, Dorota Koczkodaj1

  • 1Department of Cancer Genetics with Cytogenetic Laboratory, Medical University of Lublin, Lublin, Poland.

Acta Haematologica
|April 4, 2023
PubMed
Summary

Nurse-like cells (NLCs) in the chronic lymphocytic leukemia (CLL) microenvironment influence leukemic cell survival. The chemokine CCL3, found in both patient serum and NLC cultures, correlates with disease progression and prognostic factors.

Keywords:
CCL3Chronic lymphocytic leukemiaNurse-like cells

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Area of Science:

  • Hematology
  • Cancer Biology
  • Immunology

Background:

  • Chronic lymphocytic leukemia (CLL) development involves both genetic changes and microenvironmental signals.
  • Nurse-like cells (NLCs) are key components of the CLL microenvironment, interacting with leukemic cells via chemokines.
  • These interactions can affect leukemic cell survival by interfering with programmed cell death.

Purpose of the Study:

  • To analyze microenvironmental factors impacting leukemic cell survival in CLL.
  • To investigate the association of selected molecules (IL-8, CCL3, JAG1, CD163, BIRC5) with clinical, cytogenetic, and molecular parameters of CLL.
  • To assess the expression of these molecules in CLL patient serum and NLC culture medium.

Main Methods:

  • Long-term NLC cultures were established from 34 CLL patients' mononuclear cells.
  • NLC counts were determined using light microscopy.
  • Enzyme-linked immunosorbent assays (ELISAs) quantified IL-8, CCL3, sBIRC5, sCD163, and sJAG1 in serum and culture medium.

Main Results:

  • Significant differences in IL-8, sBIRC5, CCL3, sCD163, and sJAG1 concentrations were observed between patient serum and NLC culture medium.
  • Higher concentrations of IL-8, CCL3, and JAG1 in the culture medium confirmed the NLC microenvironment's role in their production.
  • CCL3 concentration in both serum and medium correlated with NLC count and prognostic factors (Rai stage, WBC, ZAP-70, CD38, CD5/19 expression).

Conclusions:

  • The NLC-containing microenvironment is crucial in CLL pathogenesis.
  • The chemokine CCL3 serves as a valuable indicator of the CLL microenvironment.
  • CLL progression necessitates considering both genetic factors and microenvironmental cell interactions.