Kuranda K.,French Institute of Health and Medical Research |
Kuranda K.,Institute Of Recherche Sur Le Cancer Of Lille |
Berthon C.,French Institute of Health and Medical Research |
Berthon C.,Institute Of Recherche Sur Le Cancer Of Lille |
And 9 more authors.
Journal of Cellular Biochemistry | Year: 2011
Hematopoietic cancer stem cells preserve cellular hierarchy in a manner similar to normal stem cells, yet the underlying regulatory mechanisms are poorly understood. It is known that both normal and malignant stem/progenitor cells express CD34. Here, we demonstrate that several cell lines (HL-60, U266) derived from hematopoietic malignancies contain not only CD34- but also CD34+ subpopulations. The CD34+ cells displayed a stem/progenitor-like phenotype since, in contrast to CD34- cells, they frequently underwent cellular division and rapidly formed colonies in methylcellulose-based medium. Strikingly, a constant fraction of the CD34 + and CD34- cell subpopulations, when separated, rapidly switched their phenotype. Consequently, both separated fractions could generate tumors in immunocompromised NOD/LtSz-scid/scid mice. Cultures in vitro showed that the proportion of CD34+ stem/progenitor-like cells in the population was decreased by cell-cell contact and increased by soluble factors secreted by the cells. Using cytokine arrays, we identified some of these factors, notably thymopoietin that was able to increase the proportion of CD34+ cells and overall colony-forming capacity in tested cell lines. This action of thymopoietin was conserved in mononuclear cells from bone marrow. Therefore, we propose that hematopoietic cancer cell lines containing subpopulations of CD34+ cells can provide an in vitro model for studies of cancer stem/progenitor cells. © 2011 Wiley-Liss, Inc.
Herbaux C.,Groupe Hospitalier Of Linstitut Catholique Of Lille |
Badens C.,APHM |
Poret N.,Institute Of Recherche Sur Le Cancer Of Lille |
Gardin C.,Hopital Avicenne |
And 16 more authors.
American Journal of Hematology | Year: 2015
Acquired α-thalassemia myelodysplastic syndrome (MDS) (ATMDS) is an acquired syndrome characterized by a somatic point mutation or splicing defect in the ATRX gene in patients with myeloid disorders, primarily MDS. In a large MDS patient series, the incidence of ATMDS was below 0.5%. But no large series has yet assessed the incidence of ATMDS in microcytic MDS. In this study, we focused on patients with MDS and unexplained microcytosis, which was defined as absence of iron deficiency, inflammatory disease, or history of inherited hemoglobinopathy. Our data confirm the low frequency of ATRX mutations in MDS: 0% in an unselected clinical trial cohort of 80 low risk MDS, 0.2-0.8% in a multicenter registry of 2,980 MDS and 43% of MDS with unexplained microcytosis in this same registry. In addition, we reported four novel mutations of the ATRX gene in ATMDS. This study further determines the frequency of ATRX mutations and highlights the importance of microcytosis to detect ATRX mutations within. © 2015 Wiley Periodicals, Inc.
Nibourel O.,Lille University Hospital Center |
Nibourel O.,French Institute of Health and Medical Research |
Nibourel O.,University of Lille Nord de France |
Nibourel O.,Institute Of Recherche Sur Le Cancer Of Lille |
And 38 more authors.
Blood | Year: 2010
Mutations of the ten eleven translocation 2 gene (TET2) have recently been reported in myelodysplastic syndrome and myeloproliferative neoplasms. We analyzed the incidence and prognostic value of TET2 point mutations and other genomic alterations by direct sequencing and single nucleotide polymorphism microarray analysis in 111 de novo acute myeloid leukemia, who had all achieved complete remission (CR). Mutations were observed in 19 (17%) of the 111 patients compared with 10 (27%) of 36 patients who had failed to achieve CR (P = .2). In the 111 patients who had achieved CR, TET2 alterations were only significantly associated with NPM1 mutations but not with other pretreatment characteristics. TET2 gene status was not significantly correlated with disease-free survival and overall survival, both in the entire cohort and in patients with normal karyotype. © 2010 by The American Society of Hematology.