R Schmidmaier1, K Mörsdorf, P Baumann, B Emmerich, G Meinhardt. 1. Department of Hematology and Oncology, Medizinische Klinik Innenstadt, Klinikum der Universität München, München, Germany. ralf.schmidmaier@med.uni-muenchen.de
Abstract
BACKGROUND/AIMS: Multiple myeloma is an incurable disease and patients eventually die of disease progression due to drug resistance. VLA-4 (very late antigen 4), VCAM (vascular adhesion molecule), LFA-1 (leukocyte function-associated antigen 1), and ICAM-1 (intercellular adhesion molecule 1)-mediated adhesion of myeloma cells to bone marrow stromal cells induces primary multidrug resistance in vitro. Based on these preclinical data we hypothesized that myeloma cells with strong adhesion - due to strong expression of adhesion molecules on the cell surface - are selected by chemotherapy in patients. To prove this hypothesis we determined the expression levels of adhesion molecules in 31 multiple myeloma patients by flow cytometry. METHODS: A 3-color stain with CD38, CD138 and antibodies against VLA-4, ICAM-1, LFA-1, and VCAM was performed. The patients were either at diagnosis (chemo-naive; n=17) or at relapse (pre-treated; n=15). Furthermore, the response to the next chemotherapy of chemo-naive patients was correlated with the expression levels of adhesion molecules. RESULTS: ICAM-1, VLA-4, and VCAM expression was higher in pre-treated patients than in chemo-naive patients and the expression levels increased with the number of chemotherapy regimens. Primarily multidrug-resistant patients had significantly higher expression levels of VLA-4 and ICAM-1 than responders. CONCLUSION: This study suggests that multiple myeloma cells expressing high levels of VLA-4 and ICAM-1 are drug resistant and that such a subpopulation of cells is selected by chemotherapy.
BACKGROUND/AIMS: Multiple myeloma is an incurable disease and patients eventually die of disease progression due to drug resistance. VLA-4 (very late antigen 4), VCAM (vascular adhesion molecule), LFA-1 (leukocyte function-associated antigen 1), and ICAM-1 (intercellular adhesion molecule 1)-mediated adhesion of myeloma cells to bone marrow stromal cells induces primary multidrug resistance in vitro. Based on these preclinical data we hypothesized that myeloma cells with strong adhesion - due to strong expression of adhesion molecules on the cell surface - are selected by chemotherapy in patients. To prove this hypothesis we determined the expression levels of adhesion molecules in 31 multiple myeloma patients by flow cytometry. METHODS: A 3-color stain with CD38, CD138 and antibodies against VLA-4, ICAM-1, LFA-1, and VCAM was performed. The patients were either at diagnosis (chemo-naive; n=17) or at relapse (pre-treated; n=15). Furthermore, the response to the next chemotherapy of chemo-naive patients was correlated with the expression levels of adhesion molecules. RESULTS: ICAM-1, VLA-4, and VCAM expression was higher in pre-treated patients than in chemo-naive patients and the expression levels increased with the number of chemotherapy regimens. Primarily multidrug-resistant patients had significantly higher expression levels of VLA-4 and ICAM-1 than responders. CONCLUSION: This study suggests that multiple myeloma cells expressing high levels of VLA-4 and ICAM-1 are drug resistant and that such a subpopulation of cells is selected by chemotherapy.
Authors: Daniel W Sherbenou; Yang Su; Christopher R Behrens; Blake T Aftab; Olivia Perez de Acha; Megan Murnane; Shelby C Bearrows; Byron C Hann; Jeffery L Wolf; Thomas G Martin; Bin Liu Journal: Clin Cancer Res Date: 2020-09-11 Impact factor: 12.531
Authors: Irene M Min; Enda Shevlin; Yogindra Vedvyas; Marjan Zaman; Brian Wyrwas; Theresa Scognamiglio; Maureen D Moore; Weibin Wang; Susan Park; Spencer Park; Suraj Panjwani; Katherine D Gray; Andrew B Tassler; Rasa Zarnegar; Thomas J Fahey; Moonsoo M Jin Journal: Clin Cancer Res Date: 2017-10-12 Impact factor: 12.531
Authors: Jennifer M Scalici; Christine Harrer; Anne Allen; Amir Jazaeri; Kristen A Atkins; Karen R McLachlan; Jill K Slack-Davis Journal: Gynecol Oncol Date: 2013-12-28 Impact factor: 5.482
Authors: Tara M Tancred; Andrew R Belch; Tony Reiman; Linda M Pilarski; Julia Kirshner Journal: J Histochem Cytochem Date: 2008-11-11 Impact factor: 2.479