References of "Hermine, Olivier"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailCis-perturbation of cancer drivers by the HTLV-1/BLV proviruses is an early determinant of leukemogenesis
Rosewick, Nicolas; Durkin, Keith ULiege; Artesi, Maria ULiege et al

in Nature Communications (2017), 8

Detailed reference viewed: 45 (7 ULiège)
Peer Reviewed
See detailImproved high throughput DNA-seq based mapping of HTLV-1 integration sites: a tool to define response to treatment, ATL prognosis and guide therapeutic strategies
Marçais, Ambroise; Artesi, Maria ULiege; Durkin, Keith ULiege et al

Conference (2017)

Background Adult T-cell leukemia/lymphoma (ATL) is an aggressive CD4+ T-cell malignancy caused by HTLV-1 infection and associated with extremely poor prognosis. In France, treatment strategies mainly ... [more ▼]

Background Adult T-cell leukemia/lymphoma (ATL) is an aggressive CD4+ T-cell malignancy caused by HTLV-1 infection and associated with extremely poor prognosis. In France, treatment strategies mainly include chemotherapy, antiviral therapy and allogeneic stem cell transplantation, based on clinical subtype and therapeutic responses. Response to treatment is evaluated based on consensus criteria defined in 2009 (Tsukasaki K, Hermine O et al, JCO 2009). Although immuno-phenotyping, TCRγ rearrangement and HTLV-1 proviral load (PVL) quantification are often assayed, complete clinical remission (CR) is currently defined by morphological and cytological criteria i.e. complete blood cell counts (CBC) and the presence of abnormal lymphocytes. Given the extremely poor prognosis and high rates of early relapse, a revision of the response criteria is required, calling for improved tools that integrate specific aspects of the pathophysiology of ATL to better estimate response to treatment. Methods We retrospectively analyzed longitudinal PBMC samples from 6 ATL patients diagnosed with a leukemic subtype (5 acute and 1 chronic-aggressive) which all achieved CR upon therapy, yet relapsed after a median time of 15,9 months (range 2,4-70,7). CR was assessed by morphological and cytological criteria. An improved high throughput sequencing (HTS) based method was utilized to map and quantify the abundance of HTLV-1 genomic integration sites (IS), overcoming some of the limitations of previously published protocols. The dynamic range was increased by assaying both the 5’LTR and 3’LTRs, allowing better determination of clone abundance and revealing 5’ deletions. An enrichment step limited PCR duplicates. The addition of off-the-shelf Illumina primers simplified library multiplexing and reduced the costs to the point where the protocol could be applied to a clinical setting. Results HTS- mapping of HTLV-1 IS at diagnosis revealed in all cases a unique IS that constituted 92-99% of proviral genomes, with PVLs of 33-510%. All patients were treated and achieved CR which was characterized by normalized CBC, <5% abnormal lymphocytes and the absence of measurable tumors for >4 weeks. For 3/6 patients, the clone frequency distribution of HTLV-1 infected cells at CR was composed of multiple low abundance clones, of which the unique presumed malignant IS contributed to less than 2% of proviral genomes. In contrast, clonality analysis of the remaining 3/6 patients revealed that the relative abundance of the malignant clone detected at diagnosis remained dominant at CR (36-83% of PVL), despite clinical response criteria typical of CR and a 3-20-fold decrease in PVLs. These patients relapsed after 2.4, 2.9 and 3.4 months respectively with a dominant malignant clone >95% while patients with a polyclonal architecture showed significantly longer CR (28, 59 and 71 months). Conclusions Our observations highlight the great heterogeneity within an identical CR group, underlining the need for revisiting response criteria for ATL. Our results call for the use of this improved HTS-based method to measure HTLV-1 clonality as a tool to better estimate response to treatment, predict relapse and guide therapeutic choices in the course of treatment. [less ▲]

Detailed reference viewed: 45 (8 ULiège)
Full Text
Peer Reviewed
See detailReducing the global burden of HTLV-1 infection: An agenda for research and action
Willems, Luc ULiege; Hasegawa, Hideki; Accolla, Roberto et al

in Antiviral Research (2016), 137(2017), 41-48

Even though an estimated 10e20 million people worldwide are infected with the oncogenic retrovirus, human T-lymphotropic virus type 1 (HTLV-1), its epidemiology is poorly understood, and little effort has ... [more ▼]

Even though an estimated 10e20 million people worldwide are infected with the oncogenic retrovirus, human T-lymphotropic virus type 1 (HTLV-1), its epidemiology is poorly understood, and little effort has been made to reduce its prevalence. In response to this situation, the Global Virus Network launched a taskforce in 2014 to develop new methods of prevention and treatment of HTLV-1 infection and promote basic research. HTLV-1 is the etiological agent of two life-threatening diseases, adult T-cell leukemia and HTLV-associated myelopathy/tropical spastic paraparesis, for which no effective therapy is currently available. Although the modes of transmission of HTLV-1 resemble those of the more familiar HIV-1, routine diagnostic methods are generally unavailable to support the prevention of new infections. In the present article, the Taskforce proposes a series of actions to expand epidemiological studies; increase research on mechanisms of HTLV-1 persistence, replication and pathogenesis; discover effective treatments; and develop prophylactic and therapeutic vaccines. [less ▲]

Detailed reference viewed: 26 (5 ULiège)
Full Text
Peer Reviewed
See detailHTLV-1/BLV antisense-RNA dependent host gene perturbation in pre-leukemic and leukemic clones
Rosewick, Nicolas; Durkin, Keith ULiege; Marçais, Ambroise et al

in Retrovirology (2015, August 28), 12(1),

Detailed reference viewed: 26 (2 ULiège)
Full Text
Peer Reviewed
See detailImproving the methodology for the detection of proviral integration sites in the host genome via high throughput sequencing.
Durkin, Keith ULiege; Artesi, Maria ULiege; Rosewick, Nicolas et al

in Retrovirology (2015, August 28), 12(1),

Detailed reference viewed: 11 (1 ULiège)
Peer Reviewed
See detailExploring the Deltaretrovirus Tumor Transcriptome: Lessons from RNA-Seq
Rosewick, Nicolas; Durkin, Keith ULiege; Thys, Wannes et al

Conference (2014, June)

Detailed reference viewed: 5 (0 ULiège)
Full Text
Peer Reviewed
See detailUpfront allogeneic stem cell transplantation after reduced-intensity/nonmyeloablative conditioning for patients with myelodysplastic syndrome : a study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire
Damaj, Gandhi; Mohty, Mohammad; Robin, Marie et al

in Biology of Blood & Marrow Transplantation (2014), 20

Cytoreduction before allogeneic stem cell transplantation (allo-SCT) for patients with myelodysplastic syndromes remains a debatable issue. After excluding patients who had received preconditioning ... [more ▼]

Cytoreduction before allogeneic stem cell transplantation (allo-SCT) for patients with myelodysplastic syndromes remains a debatable issue. After excluding patients who had received preconditioning induction chemotherapy, we analyzed 128 consecutive patients with myelodysplastic syndrome who received reducedintensity or nonmyeloablative conditioning (RIC/NMA) allo-SCT. Among them, 40 received azacitidine (AZA) before transplant (AZA group) and 88 were transplanted up front (best supportive care [BSC] group). At diagnosis, 55 patients had intermediate 2 or high-risk scores per the International Prognostic Scoring System and 33 had a high cytogenetic risk score. Progression to a more advanced disease before allo-SCT was recorded in 22 patients. Source of stem cells were blood (n ¼ 112) or marrow (n ¼ 16) from sibling (n ¼ 78) or HLA-matched unrelated (n ¼ 50) donors. With a median follow-up of 60 months, 3-year overall survival, relapse-free survival, cumulative incidence of relapse, and nonrelapse mortality were, respectively, 53% versus 53% (P ¼ .69), 37% versus 42% (P ¼ .78), 35% versus 36% (P ¼ .99), and 20% versus 23% (P ¼ .74), for the AZA group and BSC group, respectively. Multivariate analysis confirmed the absence of statistical differences in outcome between the AZA and BSC groups, after adjusting for potential confounders using the propensity score approach. The absence of cytoreduction before RIC/NMA allo-SCT did not seem to alter the outcome. However, our results emphasize the need to perform prospective protocols to delineate the role of debulking strategy and to identify subsets of patients who may benefit from this approach. [less ▲]

Detailed reference viewed: 39 (0 ULiège)
Full Text
Peer Reviewed
See detailHTLV-1 positive and negative T cells cloned from infected individuals display telomerase and telomere genes deregulation that predominate in activated but untransformed CD4+ T cells.
Zane, Linda; Sibon, David; CAPRARO, Valérie ULiege et al

in International Journal of Cancer = Journal International du Cancer (2012), 131(4), 821-33

Untransformed HTLV-1 positive CD4(+) cells from infected individuals are selected for expressing tax and displaying morphological features consistent with telomere dysfunctions. We show that in resting ... [more ▼]

Untransformed HTLV-1 positive CD4(+) cells from infected individuals are selected for expressing tax and displaying morphological features consistent with telomere dysfunctions. We show that in resting HTLV-1 positive CD4(+) cells cloned from patients, hTERT expression parallels tax expression and cell cycling. Upon activation, these cells dramatically augment tax expression, whereas their increase in telomerase activity is about 20 times lower than that of their uninfected counterpart. Activated HTLV-1 positive CD4(+) but not uninfected CD4(+) or CD8(+) clones also repress the transcription of TRF1, TPP1, TANK1, POT1, DNA-PKc and Ku80. Both infected and uninfected lymphocytes from infected individuals shared common telomere gene deregulations toward a pattern consistent with premature senescence. ATLL cells displayed the highest telomerase activity (TA) whereas recovered a telomere gene transcriptome close to that of normal CD4(+) cells. In conclusion HTLV-1-dependent telomere modulations seem involved in clonal expansion, immunosuppression, tumor initiation and progression. [less ▲]

Detailed reference viewed: 24 (1 ULiège)
Full Text
Peer Reviewed
See detailHuman bone marrow adipocytes block granulopoiesis through neuropilin-1-induced granulocyte colony-stimulating factor inhibition.
Belaid-Choucair, Zakia ULiege; Lepelletier, Yves; Poncin, Géraldine ULiege et al

in Stem Cells (2008), 26(6), 1556-64

Adipocytes are part of hematopoietic microenvironment, even though up to now in humans, their role in hematopoiesis is still questioned. We have previously shown that accumulation of fat cells in femoral ... [more ▼]

Adipocytes are part of hematopoietic microenvironment, even though up to now in humans, their role in hematopoiesis is still questioned. We have previously shown that accumulation of fat cells in femoral bone marrow (BM) coincides with increased expression of neuropilin-1 (NP-1), while it is weakly expressed in hematopoietic iliac crest BM. Starting from this observation, we postulated that adipocytes might exert a negative effect on hematopoiesis mediated through NP-1. To test this hypothesis, we set up BM adipocytes differentiated into fibroblast-like fat cells (FLFC), which share the major characteristics of primitive unilocular fat cells, as an experimental model. As expected, FLFCs constitutively produced macrophage colony stimulating factor and induced CD34(+) differentiation into macrophages independently of cell-to-cell contact. By contrast, granulopoiesis was hampered by cell-to-cell contact but could be restored in transwell culture conditions, together with granulocyte colony stimulating factor production. Both functions were also recovered when FLFCs cultured in contact with CD34(+) cells were treated with an antibody neutralizing NP-1, which proved its critical implication in contact inhibition. An inflammatory cytokine such as interleukin-1 beta or dexamethasone modulates FLFC properties to restore granulopoiesis. Our data provide the first evidence that primary adipocytes exert regulatory functions during hematopoiesis that might be implicated in some pathological processes. Disclosure of potential conflicts of interest is found at the end of this article. [less ▲]

Detailed reference viewed: 148 (28 ULiège)
Full Text
Peer Reviewed
See detailL’érythropoïèse tardive : une mort avortée ?
Courtois, Geneviève; Vandekerchove, julie; Dussiot, Michael et al

in Hématologie (2007), 13(6), 400-408

La survie et la prolifération des progéniteurs et précurseurs érythroïdes se trouvent sous le contrôle de l’érythropoïétine (Epo), qui est le principal régulateur de l’érythropoïèse. La différenciation ... [more ▼]

La survie et la prolifération des progéniteurs et précurseurs érythroïdes se trouvent sous le contrôle de l’érythropoïétine (Epo), qui est le principal régulateur de l’érythropoïèse. La différenciation érythroïde s’effectue sous la dépendance du facteur de transcription GATA-1 qui active l’expression des gènes de différenciation et de survie. La production des globules rouges est finement régulée par l’inhibition ou au contraire par l’induction de l’apoptose des progéniteurs et des précurseurs érythroïdes. La baisse du taux d’Epo circulante ou l’induction de la voie Fas aboutissent à l’activation de la caspase-3 qui entraîne la protéolyse de GATA-1, l’arrêt de maturation et l’apoptose des érythroblastes immatures. Nous avons montré qu’une activation transitoire de la caspase-3 par la voie mitochondriale est indispensable à la maturation érythroïde. Dans ce contexte, la protéine chaperonne hsp70 joue un rôle majeur en protégeant GATA-1 du clivage par la caspase-3. La différenciation terminale est caractérisée par une réduction progressive du volume cellulaire et du noyau associée à une condensation de la chromatine. Ces changements morphologiques présentent certaines similitudes avec ceux observés dans les cellules en cours d’apoptose. L’énucléation s’effectue ensuite au sein d’îlots érythroblastiques constitués d’un macrophage central étroitement associé par des molécules d’adhérence à des érythroblastes en cours de maturation. La membrane de l’érythroblaste perd progressivement son affinité pour le macrophage alors que le noyau reste fixé, ce qui permet l’énucléation et la phagocytose du noyau par le macrophage. Les réticulocytes ainsi formés vont compléter leur maturation en perdant leurs organelles et en remodelant leur membrane. Nos études suggèrent que le devenir des précurseurs érythroïdes (apoptose versus différenciation) est déterminé par le choix des cibles clivées par les caspases. Si la fonction du clivage de certaines protéines telles que la lamine B ou acinus est bien connue, l’identité et la fonction des autres cibles clivées par les caspases au cours de la maturation terminale restent à déterminer. [less ▲]

Detailed reference viewed: 110 (0 ULiège)
Full Text
Peer Reviewed
See detailHuman erythroleukemia: is the two-hit model of mouse leukemogenesis valid in human disease?
Coulon, Séverine; Vandekerckhove, Julie; Dussiot, Michael et al

in Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K (2007)

Detailed reference viewed: 46 (0 ULiège)
Full Text
Peer Reviewed
See detailPrognostic Significance of bcl-2 Protein Expression in Aggressive Non-Hodkin's Lymphoma
Hermine, Olivier; Haioun, Corinne; Lepage, Eric et al

in Blood (1996)

Detailed reference viewed: 28 (3 ULiège)