Andrei Tchirkov
Centre national de la recherche scientifique
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Featured researches published by Andrei Tchirkov.
Medical and Pediatric Oncology | 1998
Andrei Tchirkov; Justyna Kanold; M. Giollant; P. Halle-Haus; Marc Berger; Chantal Rapatel; Patrick Lutz; Christophe Bergeron; Dominique Plantaz; Jean-Pierre Vannier; J.-L. Stephan; M. Favrot; Pierre Bordigoni; P. Malet; G. Briançon; François Demeocq
BACKGROUND Autologous peripheral blood stem cell (PBSCs) are frequently used to reconstitute hematopoiesis following administration of megatherapy in children with advanced stage IV neuroblastoma. Some centers prefer the use of autografts enriched for CD34+ progenitor cells because the positive selection procedure is believed to reduce indirectly tumor cell contamination. PROCEDURES In this study, we monitored the efficiency of tumor cell purging following CD34 selection in PBSCs from seven patients with advanced neuroblastoma by using a highly sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, Amplification of tissues-specific mRNA transcript of tyrosine hydroxylase gene with nested primers enabled the detection of residual neuroblastoma cells with a sensitivity of one malignant-cell per 10(6) normals. RESULTS Using this method, contaminating tumor cells were detected in seven of nine leukapheresis products of the patients. After positive immunoselection of CD34+ cells on Ceprate column, only one of nine enriched stem cell fraction still contained tumor cells detectable by RT-PCR. In six cases, PCR positive PBSCs became PCR negative after selection. CONCLUSIONS We conclude that tumor cell contamination may be frequently detected in PBSC harvests of stage IV neuroblastoma patients by sensitive molecular analysis. The load of contaminating malignant cells might be reduced following CD34 selection.
British Journal of Haematology | 1998
Andrei Tchirkov; Michel Giollant; Françoise Tavernier; Georges BrianÇon; Olivier Tournilhac; Fabrice Kwiatkowski; Pierre Philippe; Bachra Choufi; François Demeocq; Philippe Travade; Paul Malet
There is a need for fast and sensitive methods to evaluate the response of patients with chronic myeloid leukaemia (CML) to interferon‐α (IFN‐α) therapy to complement cytogenetic analysis of Philadelphia (Ph) chromosome‐positive metaphases. We have used interphase FISH (fluorescence in situ hybridization) and competitive RT‐PCR (reverse transcriptase‐polymerase chain reaction) techniques for detection of BCR‐ABL‐positive cells to measure suppression of leukaemic clone in a series of 51 follow‐up samples from 24 CML patients undergoing IFN‐α treatment. Interphase FISH analysis of the malignant clone in bone marrow using BCR and ABL probes was found to be highly correlated to conventional G‐banding metaphase examination (r = 0.98). RT‐PCR quantification of BCR‐ABL mRNA transcripts in blood also showed a high degree of concordance with the proportion of Ph‐positive metaphases (r = 0.93). In addition, the degree of cytogenetic response did not influence the equivalence between karyotype analysis and molecular methods. We concluded that interphase FISH and competitive RT‐PCR provide reliable information on residual tumour burden and response to IFN‐α in CML patients. These molecular methods may significantly improve the efficiency of residual disease monitoring during IFN‐α therapy of CML.
Journal of Hematotherapy & Stem Cell Research | 2003
Andrei Tchirkov; Catherine Paillard; Pascale Halle; Frédéric Bernard; Pierre Bordigoni; Philippe Vago; François Demeocq; Justyna Kanold
Molecular detection of tumor cells is the most sensitive approach to study residual disease in bone marrow (BM), peripheral blood (PB), and peripheral blood stem cell (PBSC) autografts from children with metastatic neuroblastoma (NB). We have developed a real-time PCR assay that allows the quantification of tyrosine hydroxylase (TH) mRNA, a tissue-specific marker of neuroblasts. We investigated a total of 165 BM, PB, and PBSC samples from 30 children over 1 year of age with stage IV NB and correlated the findings with disease status and patient survival. The levels of TH mRNA agreed well with clinical status and were significantly different across the groups that included samples obtained from patients at diagnosis, after three cycles of chemotherapy, in complete or very good partial remission and at relapse. We found that overall survival was significantly worse for patients with >1000 TH copies in BM after initial chemotherapy (p=0.0075). In 57% of cases, autologous PBSC harvests were found to be contaminated by neuroblasts, the level of TH >500 copies being associated with a decreased survival (p=0.003). In addition, molecular quantification enabled an estimation of tumor depletion in contaminated autografts using CD34 selection (median, 3 logs). In conclusion, quantification of minimal residual disease in metastatic NB using real-time RT-PCR for TH mRNA appears to be of potential clinical value. Further studies are needed to ascertain prognostic implications of molecular analysis of residual disease.
Medical and Pediatric Oncology | 2000
Justyna Kanold; Karima Yakouben; Andrei Tchirkov; A.-S. Carret; Jean-Pierre Vannier; Edouard LeGall; Pierre Bordigoni; François Demeocq
BACKGROUND This is the first report of the long-term results of CD34(+) cell transplantation in children with neuroblastoma. We investigated the hematologic and immune recovery, posttransplant morbidity, and clinical outcome of these children. PROCEDURE Twenty-three children with advanced neuroblastoma had PBPCs (20 patients) or BM (3 patients) collected, followed by CD34(+) cell selection on Ceprate column. The purge of residual neuroblastoma cells was evaluated using an RT-PCR for tyrosine hydroxylase (TH) mRNA assay. Reinfusion of CD34(+) cells followed busulfan + melphalan myeloablative chemotherapy. RESULTS A median of 2.9 x 10(6) CD34(+) cells/kg was reinjected. Median days to achieve ANC > 0.5 x 10(9)/liter and platelets > 50 x 10(9)/liter were 13 (range 9-33) and 59 (range 22-259), respectively. Circulating T cells were primarily CD4(-)/CD8(+) with fewer than 0.2 10(9)CD4(+) cells/liter throughout the first 6 months. CD19(+) cells and CD56(+) cells were not detectable up to day +35 posttransplant. At 1 year posttransplant, 16 evaluable patients had stable hematopoiesis with 2.3 x 10(9) ANC/liter (range 0.8-4.1), 1.4 x 10(9) lymphocytes/liter (range 0.5- 2.0) and 251 x 10(9) PLT/liter (range 35-490). After the completion of hematopoietic reconstitution, six events of severe septicemia/septic shock were noted. Six children had severe VZV infections, and 2 had EBV-associated lymphoproliferation. Thirteen patients are alive with a median follow-up of 40 months (range 2-54). Ten patients have died; 8 relapsed or developed progressive disease, 1 died from nondocumented pneumopathy at day 56, and 1 developed AML-M4 at 3 years posttransplant. CONCLUSIONS In children, CD34(+) cell transplantation can be accomplished with a reduction of neuroblastoma cell inoculum in the selected graft as assessed by RT-PCR analysis. CD34(+) cell grafts provide successful neutrophil reconstitution. However, delayed platelet recovery, persistent decrease in CD4(+) lymphocyte levels and a high incidence of serious and life-threatening late infections were observed in these children. There remains a critical need to evaluate any real clinical benefit of CD34(+) cell autografts in neuroblastoma patients.
Radiation Research | 2000
Claude Dionet; Andrei Tchirkov; Jean Pierre Alard; Jack Arnold; Joël Dhermain; Maryse Rapp; Véronique Bodez; Jean-Claude Tamain; Isabelle Monbel; Paul Malet; Fabrice Kwiatkowski; Denise Donnarieix; Annie Veyre; Pierre Verrelle
Abstract Dionet, C., Tchirkov, A., Alard, J-P., Arnold, J., Dhermain, J., Rapp, M., Bodez, V., Tamain, J-C., Monbel, I., Malet, P., Kwiatkowski, F., Donnarieix, D., Veyre, A. and Verrelle, P. Effects of Low-Dose Neutrons Applied at Reduced Dose Rate on Human Melanoma Cells. Human melanoma cells that are resistant to γ rays were irradiated with 14 MeV neutrons given at low doses ranging from 5 cGy to 1.12 Gy at a very low dose rate of 0.8 mGy min–1 or a moderate dose rate of 40 mGy min–1. The biological effects of neutrons were studied by two different methods: a cell survival assay after a 14-day incubation and an analysis of chromosomal aberrations in metaphases collected 20 h after irradiation. Unusual features of the survival curve at very low dose rate were a marked increase in cell killing at 5 cGy followed by a plateau for survival from 10 to 32.5 cGy. The levels of induced chromosomal aberrations showed a similar increase for both dose rates at 7.5 cGy and the existence of a plateau at the very low dose rate from 15 to 30 cGy. The existence of a plateau suggests that a repair process after low-dose neutrons might be induced after a threshold dose of 5–7.5 cGy which compensates for induced damage from doses as high as 32.5 cGy. These findings may be of interest for understanding the relative biological effectiveness of neutrons and the effects of environmental low-dose irradiation.
Leukemia | 2008
L Véronèse; Olivier Tournilhac; Pierre Verrelle; Frederic Davi; Guillaume Dighiero; E Chautard; R Veyrat-Masson; F Kwiatkowski; Carole Goumy; P Vago; P Travade; Andrei Tchirkov
Low MCL-1 mRNA expression correlates with prolonged survival in B-cell chronic lymphocytic leukemia
Journal of Neuro-oncology | 2002
Jean-Jacques Dubost; Christine Rolhion; Andrei Tchirkov; Suzanne Bertrand; Jacques Chassagne; Annie Dosgilbert; Pierre Verrelle
We investigated the production of interleukin 6 (IL-6) by a radioresistant human glioblastoma cell line G5 after single radiation events of 3, 6 and 9 Gy. The total cell number and IL-6 concentration in culture supernatant were assessed 24–96 h after irradiation. The radiation impeded or stopped G5 cell growth in a dose-dependent manner, but unexpectedly did not affect the IL-6 concentration in cell culture media that increased in the same range as in non-irradiated cultures. Furthermore, using flow cytometry, we found that the IL-6 positive cells expansion was unaffected by radiation. These findings suggested that this small (about 1%) fraction of G5 cells, constitutively producing IL-6, is highly radioresistant.
Leukemia | 2006
Andrei Tchirkov; Jean-Louis Couderc; Bernard Perissel; Carole Goumy; Aline Regnier; Nancy Uhrhammer; Pierre Verrelle; Marc Berger
A small proportion of patients with chronic myeloid leukemia (CML) express unusual types of BCR-ABL transcript. In a recent paper, Demehri et al1 pointed out that a BCR-ABL transcript with an e8a2 junction may be more frequent than other BCR-ABL mRNA variants. Moreover, a review of eight so far described cases suggested that e8a2-positive CML might be more aggressive than CML with typical e13a2 and e14a2 BCR-ABL mRNAs. We report here a novel form of e8a2 BCR-ABL transcript in a CML patient who was treated with imatinib and monitored using real-time RT-PCR.
Radiation Research | 2002
Jean-Pierre Alard; Véronique Bodez; Andrei Tchirkov; Marie-Laure Nénot; Jack Arnold; Sylvain Crespin; Maryse Rapp; Pierre Verrelle; Claude Dionet
Abstract Alard, J. P., Bodez, V., Tchirkov, A., Arnold, J., Nénot, M. L., Crespin, S., Rapp, M., Verrelle, P. and Dionet, C. Simulation of Neutron Interactions at the Single-Cell Level. Radiat. Res. 158, 650–656 (2002). We recently reported that the exposure of cancer cells to 14 MeV neutrons at a very low dose rate (0.8 mGy min−1) produced a marked increase in cell killing at 5 cGy, followed by a plateau in survival and chromosomal damage. Simulation of the energy deposition events in irradiated cells may help to explain these unusual cell responses. We describe here a Monte Carlo simulation code, Energy Deposition in Cells Irradiated by Neutrons (EDCIN). The procedure considered the experimental setup and a hemispheric cell model. The simulation data fitted the dosimetric measurements performed using tissue-equivalent ionization chambers, Geiger-Müller counters, fission chambers, and silicon diodes. The simulation showed that 80% of the energy deposited in a single cell came from the interactions of neutrons outside the cell and only 20% came from neutron interactions inside the cell. Thus the “external” interactions that result in the production of recoil protons and secondary electrons may induce most of the biological damage, which may be repaired efficiently at low dose rate. The repair process may be triggered from a threshold level of damage, which would explain an initial increase cell death due to unrepaired sublethal damage, and then may compensate for induced damage, resulting in the plateaus.
Experimental Hematology | 2003
Nathalie Boiret; Chantal Rapatel; Stéphane Boisgard; Sabine Charrier; Andrei Tchirkov; Caroline Bresson; Lionel Camilleri; Juliette Berger; Laurent Guillouard; Jean-Jacques Guérin; Pascale Pigeon; Jacques Chassagne; Marc Berger