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1.
Leukemia ; 31(12): 2702-2708, 2017 12.
Article de Anglais | MEDLINE | ID: mdl-28663577

RÉSUMÉ

Myelodysplastic syndromes (MDS) represent a heterogeneous group of hematological clonal disorders. Here, we have tested the bone marrow (BM) cells from 38 MDS patients covering all risk groups in two immunodeficient mouse models: NSG and NSG-S. Our data show comparable level of engraftment in both models. The level of engraftment was patient specific with no correlation to any specific MDS risk group. Furthermore, the co-injection of mesenchymal stromal cells (MSCs) did not improve the level of engraftment. Finally, we have developed an in vitro two-dimensional co-culture system as an alternative tool to in vivo. Using our in vitro system, we have been able to co-culture CD34+ cells from MDS patient BM on auto- and/or allogeneic MSCs over 4 weeks with a fold expansion of up to 600 times. More importantly, these expanded cells conserved their MDS clonal architecture as well as genomic integrity.


Sujet(s)
Cellules de la moelle osseuse/anatomopathologie , Syndromes myélodysplasiques/anatomopathologie , Animaux , Marqueurs biologiques , Transplantation de moelle osseuse , Aberrations des chromosomes , Modèles animaux de maladie humaine , Femelle , Expression des gènes , Gènes rapporteurs , Hétérogreffes , Humains , Immunophénotypage , Mâle , Cellules souches mésenchymateuses , Souris , Souris knockout , Syndromes myélodysplasiques/diagnostic , Syndromes myélodysplasiques/génétique , Syndromes myélodysplasiques/métabolisme
2.
Leukemia ; 29(5): 1084-91, 2015 May.
Article de Anglais | MEDLINE | ID: mdl-25627637

RÉSUMÉ

In 2008, a European registry of relapsed acute promyelocytic leukemia was established by the European LeukemiaNet. Outcome data were available for 155 patients treated with arsenic trioxide in first relapse. In hematological relapse (n=104), 91% of the patients entered complete hematological remission (CR), 7% had induction death and 2% resistance, 27% developed differentiation syndrome and 39% leukocytosis, whereas no death or side effects occurred in patients treated in molecular relapse (n=40). The rate of molecular (m)CR was 74% in hematological and 62% in molecular relapse (P=0.3). All patients with extramedullary relapse (n=11) entered clinical and mCR. After 3.2 years median follow-up, the 3-year overall survival (OS) and cumulative incidence of second relapse were 68% and 41% in hematological relapse, 66% and 48% in molecular relapse and 90 and 11% in extramedullary relapse, respectively. After allogeneic or autologous transplantation in second CR (n=93), the 3-year OS was 80% compared with 59% without transplantation (n=55) (P=0.03). Multivariable analysis demonstrated the favorable prognostic impact of first remission duration ⩾1.5 years, achievement of mCR and allogeneic or autologous transplantation on OS of patients alive after induction (P=0.03, P=0.01, P=0.01) and on leukemia-free survival (P=0.006, P<0.0001, P=0.003), respectively.


Sujet(s)
Antinéoplasiques/usage thérapeutique , Composés de l'arsenic/usage thérapeutique , Leucémie aiguë promyélocytaire/traitement médicamenteux , Oxydes/usage thérapeutique , Adolescent , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Trioxyde d'arsenic , Différenciation cellulaire , Enfant , Enfant d'âge préscolaire , Survie sans rechute , Europe , Femelle , Humains , Coopération internationale , Leucémie aiguë promyélocytaire/anatomopathologie , Mâle , Adulte d'âge moyen , Études prospectives , Récidive , Enregistrements , Résultat thérapeutique , Jeune adulte
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