B-chronic lymphocytic leukemia chemoresistance involves innate and acquired leukemic side population cells

Autor: Guy Laurent, S Kheirallah, Brassac M, Loic Ysebaert, Emilie Gross, Jean-Jacques Fournié, Stéphanie Struski, Fatima-Ezzahra L'Faqihi-Olive, Anne Quillet-Mary
Přispěvatelé: Centre de Physiopathologie de Toulouse-Purpan (INSERM U563 - CNRS UMR1037), Centre National de la Recherche Scientifique (CNRS)-Centre de lutte contre le cancer (CLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut Claudius Regaud, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, IFR150, Laboratoire d'Hématologie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service d'hématologie [Hôpital Purpan, Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse]
Rok vydání: 2010
Předmět:
Cancer Research
medicine.medical_specialty
medicine.medical_treatment
Chronic lymphocytic leukemia
[SDV.CAN]Life Sciences [q-bio]/Cancer
Cell Separation
03 medical and health sciences
Antibodies
Monoclonal
Murine-Derived
0302 clinical medicine
Side population
immune system diseases
hemic and lymphatic diseases
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Bendamustine Hydrochloride
Humans
Coloring Agents
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
0303 health sciences
Chemotherapy
Hematology
business.industry
medicine.disease
Flow Cytometry
ADP-ribosyl Cyclase 1
Leukemia
Lymphocytic
Chronic
B-Cell
Recombinant Proteins
3. Good health
Fludarabine
Leukemia
Phenotype
Oncology
Drug Resistance
Neoplasm
030220 oncology & carcinogenesis
Immunology
Monoclonal
Nitrogen Mustard Compounds
[SDV.IMM]Life Sciences [q-bio]/Immunology
Interleukin-2
Rituximab
business
Vidarabine
medicine.drug
Zdroj: Leukemia
Leukemia, Nature Publishing Group: Open Access Hybrid Model Option B, 2010, 24 (11), pp.1885-1892. ⟨10.1038/leu.2010.176⟩
ISSN: 1476-5551
0887-6924
DOI: 10.1038/leu.2010.176⟩
Popis: B-cell chronic lymphocytic leukemia (B-CLL) therapy remains unsatisfactory due to repeated resurgences of the chemoresistant disease. In this study, we investigated the basis of this chemoresistance by applying the 'side population' (SP) analysis to blood samples from B-CLL patients. We report the existence of few natural SP cells, which harbors phenotypic and cytogenetic hallmarks of B-CLL in most patients with this disease (n=22). SP cells appeared resistant to conventional B-CLL treatments, such as Fludarabine, Bendamustin or Rituximab. Indeed, treatment with Fludarabine (16/18 cases) or Bendamustin (5/7 cases) resulted in complete elimination of non-SP, whereas cells displaying the SP phenotype were the only surviving. Although some B-CLL SP cells were innately chemoresistant, chemotherapy by Fludarabine selected not only innate SP cells but also induced some acquired SP cells, which arose from non-SP by drug-driven evolution. This SP selection by chemotherapeutic treatments is further supported by the overall increase of the SP percentage in patients who experienced chemotherapy in the preceding year. Functionally, proliferative stimulation of SP cells was able to partially replenish in vitro the non-SP cell compartment of the B-CLL disease. The chemoresistance of B-CLL relies, in our model, on the cellular heterogeneity of B-CLL SP cells and on their regenerating dynamics.
Databáze: OpenAIRE
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