Molecular pathogenesis of chronic lymphocytic leukemia

Alexey Danilov, Olga V. Danilova, Andreas K. Klein, Brigitte T. Huber

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Chronic lymphocytic leukemia (CLL) is unique among malignancies since it represents an accumulation of B-lymphocytes resistant to apoptosis. Several factors are thought to confer this unusual feature to a CLL B-cell. Misbalance between cytoplasmic pro-survival and pro-death molecules, such as Bcl-2, Mcl-1 and alike, appears to be one of the key factors defining B-cell longevity. Autocrine pathways, such as vascular endothelial growth factor-receptor pathway, also contribute to survival. The role of B-cell receptor (BCR) is less straightforward. In the last decade it became clear that CLL does not constitute a uniform disease, but, based on the prevalence of mutations in the BCR heavy chain (IgVH), can be classified into two distinct subgroups. Several molecular markers correlate with IgVH mutations. Some of them, like zeta-chain associated protein kinase, are also involved in BCR signaling and influence cell cycle. Yet the primary pathogenic event leading to increased proliferation and survival in CLL is difficult to ascertain. Molecules involved in BCR signaling pathways and cytoplasmic pro-survival players probably act in concert to confer resistance to apoptosis. In this respect, the role of the B-CLL environment, which includes nurse-like cells and T-cells, cannot be underestimated. Nurse-like cells provide stimuli necessary for perpetuation of life in CLL. On the other hand, abnormal T-cell function, whether it is excessive immunosuppression delivered by regulatory T-cells or insufficient anti-tumor immunity rendered by T-helpers, allows malignant CLL cells to go unnoticed by the cellular immune system.

Original languageEnglish (US)
Pages (from-to)665-675
Number of pages11
JournalCurrent Molecular Medicine
Volume6
Issue number6
DOIs
StatePublished - Sep 2006
Externally publishedYes

Fingerprint

B-Cell Chronic Lymphocytic Leukemia
T-cells
Cells
B-Lymphocytes
Apoptosis
Vascular Endothelial Growth Factor Receptor
Molecules
Lymphocytes
Immune system
Protein Kinases
Tumors
Nurses
T-Lymphocytes
Mutation
Regulatory T-Lymphocytes
Immunosuppression
Immune System
Immunity
Neoplasms
Cell Cycle

Keywords

  • Apoptosis
  • Bcl-2
  • Chromosomal aberrations
  • Endoplasmic reticulum (ER) stress
  • Nurse-like cells
  • VEGF-R

ASJC Scopus subject areas

  • Biochemistry

Cite this

Molecular pathogenesis of chronic lymphocytic leukemia. / Danilov, Alexey; Danilova, Olga V.; Klein, Andreas K.; Huber, Brigitte T.

In: Current Molecular Medicine, Vol. 6, No. 6, 09.2006, p. 665-675.

Research output: Contribution to journalArticle

Danilov, Alexey ; Danilova, Olga V. ; Klein, Andreas K. ; Huber, Brigitte T. / Molecular pathogenesis of chronic lymphocytic leukemia. In: Current Molecular Medicine. 2006 ; Vol. 6, No. 6. pp. 665-675.
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