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Forschungsdatenbank PMU-SQQUID

Differential bone marrow homing capacity of VLA-4 and CD38 high expressing chronic lymphocytic leukemia cells.
Brachtl, G; Sahakyan, K; Denk, U; Girbl, T; Alinger, B; Hofbauer, SW; Neureiter, D; Hofbauer, JP; Egle, A; Greil, R; Hartmann, TN;
PLoS One. 2011; 6(8):e23758
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Brachtl Gabriele
Egle Alexander
Girbl Tamara
Greil Richard
Hartmann Tanja
Hofbauer Sebastian
Neureiter Daniel
Pinon Hofbauer Josefina

Abstract

BACKGROUND
VLA-4 and CD38 predict a poor clinical outcome in chronic lymphocytic leukemia (CLL). We used CLL samples with discordant VLA-4/CD38 risk to address their individual roles in human bone marrow infiltration (BM), CLL cell homing to murine BM, and in supportive CLL cell-stromal cell interactions.
VLA-4, CD38, and Ki-67 expression was measured in CLL cells from peripheral blood (PB) and bone marrow (BM) aspirates. CLL BM infiltration rates, routinely determined by Pathology, were correlated to VLA-4 and CD38 expression. Short-term homing capacity of CLL cells was evaluated by adoptive transfer experiments. CLL cell viability and adhesion in stromal cell co-culture was determined.
About 20% of CLL samples in our cohort displayed discordant VLA-4 and CD38 risk, with either high VLA-4 and low CD38 risk or vice versa. Using particularly such samples, we observed that VLA-4, and not CD38, was responsible for recirculation of CLL cells to murine BM. Human BM infiltration was also significantly higher in patients with high VLA-4 risk but not high CD38 risk. However, both molecules acted as independent prognostic markers. While both VLA-4 and CD38 expression were increased in BM-derived CLL cells, and VLA-4+ and CD38+ subpopulations showed enriched Ki-67 expression, VLA-4 did not contribute to CLL cell protection by stromal cells in vitro.
Our data argue for a prominent role of VLA-4 but not CD38 expression in the homing of CLL cells to BM niches and in human BM infiltration, but only a limited role in their protection by stromal cells.


Useful keywords (using NLM MeSH Indexing)

Animals

Antigens, CD38/blood

Antigens, CD38/metabolism*

Apoptosis

B-Lymphocytes/immunology

Bone Marrow/metabolism

Bone Marrow/pathology*

Cell Adhesion

Cell Count

Female

Humans

Immunohistochemistry

Integrin alpha4beta1/blood

Integrin alpha4beta1/metabolism*

Ki-67 Antigen/metabolism

Leukemia, Lymphocytic, Chronic, B-Cell/blood

Leukemia, Lymphocytic, Chronic, B-Cell/metabolism*

Leukemia, Lymphocytic, Chronic, B-Cell/pathology*

Leukemic Infiltration/pathology*

Lymphoid Tissue/pathology

Male

Mice

Risk Factors

Stromal Cells/pathology

Survival Analysis