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O Blanchet

Publications and source records attributed to O Blanchet.

16 recordsLinked to original sources
PubMed2005

Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics.

Idiopathic hypereosinophilic syndrome (HES) characterized by unexplained and persistent hypereosinophilia is heterogeneous and comprises several entities: a myeloproliferative form where myeloid lineages are involved with the interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA genes, the latter acquiring increased tyrosine kinase activity. And a lymphocytic variant, where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T-cell clone. We performed molecular characterization of HES in 35 patients with normal karyotype by conventional cytogenetic analysis. TCRgamma gene rearrangements suggesting T clonality were seen in 11 (31%) patients, and FIP1L1-PDGFRA by RT-PCR in six (17%) of 35 patients, who showed no evidence of T-cell clonality. An elevated serum tryptase level was observed in FIP1L1-PDGFRA-positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia. Sequencing FIP1L1-PDGFRA revealed scattered breakpoints in FIP1L1-exons (10-13), whereas breakpoints were restricted to exon 12 of PDGFRA. In the 29 patients without FIP1L1-PDGFRA, no activating mutation of PDGFRA/PDGFRB was detected; however; one patient responded to imatinib. FISH analysis of the 4q12 deletion was concordant with FIP1L1-PDGFRA RT-PCR data. Further investigation of the nature of FIP1L1-PDGFRA affected cells will improve the classification of HES.

Adolescent↗
PubMed2003

A potential graft-versus-leukemia effect after allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: results from the French Bone Marrow Transplantation Society.

SUMMARY: Philadelphia chromosome (Ph) acute lymphoblastic leukemia-positive (ALL) is a subgroup of ALL with a poor prognosis. We sought to evaluate the results of allogeneic hematopoietic stem cell transplantation (HSCT) in this situation. From 1992 to 2000, 121 patients with Ph- positive ALL enrolled in one of the three main French prospective ALL chemotherapy trials and receiving allogeneic HSCT were reported to the registry of the French Society of Bone Marrow Transplantation (SFGM-TC). The median age was 35 years (range, 1-53). In all, 76 patients received HSCT in first complete remission and 45 in a more advanced disease stage. Minimal residual disease was evaluated just before the graft: 35 patients of the 52 patients in first remission had persistent BCR-ABL transcript detectable while 17 had no detectable minimal residual disease. Bone marrow and/or peripheral blood samples from 94 patients were submitted for reverse transcriptase polymerase chain reaction analysis at variable points after transplantation. Estimated 2-year survival and relapse rate for patients in CR1 were 50 and 37%, respectively, significantly better than for patients with more advanced disease (P=0.0001 and 0.01, respectively). There was no difference in survival or in relapse rates in terms of the donor used. Relapse was the most common cause of treatment failure. Hematological status at the time of transplant and the occurrence of acute graft-versus-host disease (GvHD) were the only two prognostic factors identified for relapse (P=0.02 and 0.02, respectively). Detection of BCR-ABL transcripts after transplantation had a predictive value on relapse occurrence. Finally, donor lymphocyte infusions were successfully used to treat some relapses. The graft-versus-leukemia effect of HSCT in Ph-positive ALL appears to be supported by (1) the lack of prognostic significance of pretransplant BCR-ABL transcript detection, (2) the efficacy of donor lymphocyte infusions in cases of relapse, and (3) the role of GvHD as protecting against relapse.

Acute Disease↗
PubMed1998

Deregulated expression of the TAL1 gene by t(1;5)(p32;31) in patient with T-cell acute lymphoblastic leukemia.

TAL1 gene deregulation is frequent in T-cell acute lymphoblastic leukemia (T-ALL) and can result from translocations involving 1p32 or, more frequently, from a cytogenetically undetectable interstitial deletion of chromosome 1. This study presents a case of T-ALL with a t(1;5)(p32;q31) involving TAL1, in which the breakpoint occurs approximately 10kbp 5' to the gene and leads to transcriptional activation and synthesis of a TAL1 protein, and extends the spectrum of recognized TAL1 gene translocations associated with T-ALL.

Adult↗
PubMed1997

Several cytogenetic subclones may be identified within plasma cells from patients with monoclonal gammopathy of undetermined significance, both at diagnosis and during the indolent course of this condition.

Monoclonal gammopathy of undetermined significance (MGUS) is a frequent condition in patients over 50 years old, that ultimately leads to multiple myeloma (MM) in 20% of patients after 20 to 35 years of follow-up. Little is known about cytogenetic changes associated with this condition. We studied 19 MGUS patients both at diagnosis and after 12 to 35 months of follow-up (mean = 26), using DNA content measurement of bone marrow plasma cells (BMPC), and a new interphase fluorescence in situ hybridization technique (FISH) allowing the simultaneous identification of monotypic BMPC (fluorescent anti light-chain antibodies) and the determination of the number of copies for two different chromosomes within the same PC nucleus (one biotin-labeled probe coupled next to texas red avidin and one FITC-labeled probe). At diagnosis of the MGUS, single interphase FISH showed at least one numeric chromosome change in 13 of 19 patients, after the use of centromeric probes directed against chromosomes no. 3, no. 7, no. 9, and no. 11. At follow-up, abnormalities found at diagnosis in 13 patients were still shown. Moreover, abnormalities occurred in three of the last six patients (trisomy for one to three different chromosomes), although no patient evolved into MM. Dual interphase FISH showed that some BMPC bore numeric changes with both probes tested whereas other BMPC bore abnormality with only one of the probes tested. In patients who showed trisomy for at least three different chromosomes, distribution of numeric changes within BMPC defined significant numbers of up to seven different BMPC clones. All these various clones were shown both at diagnosis and at follow-up. In every patient, these various clones differed only for the number of abnormalities they exhibited, and could be related to each other in a model of gradual acquisition of chromosome changes. Eventually, data reported here show that MGUS patients acquire slowly, gradually, but ineluctably chromosome changes, distributed within several related subclones. However, these changes are not related to transformation into MM: among the various clones coexisting within the same patient, a peculiar change, still to demonstrate, might develop and lead to overt MM.

Adult↗
PubMed1997

Successive transformation of chronic myelomonocytic leukaemia into acute myeloblastic then lymphoblastic leukaemia, both with minor-bcr rearrangement.

We report a case of chronic myelomonocytic leukaemia (CMML), which transformed first into acute myeloblastic leukaemia (AML) and then into acute lymphoblastic leukaemia (ALL). In the AML and ALL phases, chromosome analysis showed a classic Philadelphia chromosome (Ph) t(9:22)(q34:q11). Molecular studies showed breakpoint cluster region rearrangement between exons e1 and a2 compatible with a p190(bcr/abl) breakpoint as observed in Ph-positive lymphoblastic acute leukaemia. The minor (m-bcr) rearrangement was also detected during complete remission. This observation supports a multistep pathogenesis of leukaemias, and that the p190(bcr/abl) breakpoint may influence the course of the disease.

Aged↗
PubMed1996

Myelodysplastic syndrome with t(5;12)(q31;p12-p13) and eosinophilia: a pediatric case with review of literature.

PURPOSE: Myelodysplastic syndrome with chromosomal translocation t(5;12)(q31-33;p12-13) and eosinophilia is a new entity recently described. Nine cases have been described in adults. We report the first pediatric case with a long follow-up (7 years). PATIENTS AND METHODS: An 8-year-old girl presented with hyperleukocytosis, eosinophilia, and no clinical symptoms. Bone marrow investigations revealed myeloid hyperplasia and clonal chromosomal translocation t(5;12)(q31;p12-13). No treatment was prescribed, but 4 years later the white blood cell count reached 144 X 10(9)/L with immature myeloid cells and splenic enlargement. Hydroxyurea chemotherapy led to a hematopoietic remission. The patient is now 16 years old and well, >7 years after the initial diagnosis. RESULTS: The association: myelodysplastic syndrome, eosinophilia and translocation t(5;12)(q31-33;p12-13), seems to be a specific hematologic disorder. Study of cases previously reported in the literature shows the most important characteristics of this disease. However, there are still a number of questions about the disease itself (especially its treatment) and the significance of the chromosomal abnormalities. CONCLUSION: This case seems to be the first report of the disease in a child and has had the longest follow-up. Other data should be collected to improve our knowledge of this hematopoietic disorder.

Adult↗
PubMed1996

Novel DNA assay for cytomegalovirus detection: comparison with conventional culture and pp65 antigenemia assay.

We compared conventional cytomegalovirus (CMV) isolation, rapid viral culture, a CMV pp65 antigenemia assay, and a novel CMV DNA hybrid capture system (HCS). A total of 309 blood samples from individuals in different risk groups were assessed by at least two of the methods mentioned above. Leukocytes were recovered either after centrifugation in Leucosep tubes containing 1.080 Ficoll for pp65 assay or after simple differential lysis steps for DNA detection. HCS was based on DNA hybridization with a CMV RNA probe and its capture by antibodies to DNA-RNA hybrids. The CMV pp65 lower matrix protein was detected by fluorescence with c10-c11 monoclonal antibody in formalin-fixed leukocytes. Concordant results were observed for 92.9, 78.3, and 82.7% of the patients when comparing (i) viral culture and the pp65 antigenemia assay, (ii) viral culture and HCS, and (iii) the pp65 antigenemia assay and HCS, respectively. Discordant results were observed between a positive HCS result and negative culture and/or pp65 results. These results were associated with relatively low DNA levels (< 20 pg/10(6) cells) and positive viruria. In conclusion, the pp65 antigenemia assay is a rapid and reliable method of detecting CMV and is preferable to culture, but the Murex HCS appears to be more sensitive for CMV detection.

Antigens, Viral↗
PubMed1994

Multiple nuclear factors bind to novel positive and negative regulatory elements upstream of the human MHC class I gene HLA-A11.

Quantitative expression of class I genes varies widely in different tissues, during development and in some neoplastic cells. Regulatory DNA sequences controlling levels of transcription of class I genes have been characterized in the murine and swine promoters. Although some regulatory features appear to be retained in humans, most of them are not evolutionary conserved. In this study, we identify novel DNA sequences and factors which contribute to the regulation of the human HLA-A11 gene. Two activator elements (-155 to -91 and -335 to -206) and one negative element (-172 to -156), distinct from those previously described are mapped within 335 bp upstream of exon 1 of the human HLA-A11 gene. Various nuclear factors bind to these regulatory elements, some of which are cell restricted or interact with evolutionary divergent regulatory sequences of the human class I gene promoter. Two of the five DNA-binding sites characterized in this work bind at least two proteins which compete for the occupancy of their site. The identification of these new regulatory elements provides a more comprehensive basis for the understanding of physiological or pathological modulation of MHC class I transcription in humans.

Base Sequence↗
PubMed1994

Translocation t(5;12)(q31-q33;p12-p13): a non-random translocation associated with a myeloid disorder with eosinophilia.

A t(5;12)(q33;p13) translocation has been detected in two patients with myeloid disorder and eosinophilia. Six other patients with haematological disease with eosinophilia with similar translocation have been published previously. The existence of a new entity, a myeloproliferative disorder with eosinophilia and t(5;12) (q31-q33;p12-p13), is suggested by the results of the present study.

Aged↗
PubMed1993

[Iron deficiency anemia].

Iron deficiency anaemia is characterized by the conjunction of a microcytic, typically are generative anaemia and a biochemical syndrome in which sideropoenia is associated with transferrin increase. It is usually due to a chronic exsudative gastrointestinal or gynaecological bleeding. Diagnosing the mechanism of anaemia is easy in most cases, but difficulties arise from association with a pathology, such as chronic inflammatory syndrome, disturbing the haematological or biochemical data. The prognosis of iron deficiency anaemia depends on its cause. Treatment is aetiological (the cause of chronic bleeding is suppressed) and symptomatic (the body's iron reserves are quickly restored).

Anemia, Hypochromic↗
PubMed1992

Altered binding of regulatory factors to HLA class I enhancer sequence in human tumor cell lines lacking class I antigen expression.

Class I antigens encoded in the major histocompatibility complex (MHC) (HLA in man, H-2 in the mouse) play a key role in the recognition of target cells by cytolytic T lymphocytes. Tumor cells frequently do not express class I MHC molecules, which strongly suggests that down-regulation of the latter facilitates escape of tumor cells from immune surveillance. The expression of class I MHC genes is tightly regulated. An enhancer element, conserved in the promoters of mouse and human MHC genes, has been shown to be important for mouse class I MHC gene expression. At least two related regulatory factors (KBF1 and NF-kappa B) bind to this regulatory element. We have analyzed the binding of these factors in cellular extracts of 23 human tumor cell lines displaying various levels of class I mRNA and surface expression. In this panel, combined deficiency of KBF1- and NF-kappa B-like DNA-binding activities was frequent among the class I-negative cell lines and correlated with the absence of class I mRNA. A few cell lines that lack KBF1 binding activity still display NF-kappa B-like activity and express normal levels of MHC class I mRNA. These results suggest (i) that, in the absence of KBF1, NF-kappa B or a related factor promotes MHC class I gene transcription; and (ii) that a combined defect in KBF1/NF-kappa B DNA-binding activity can cause a pleiotropic defect in class I gene expression, which may facilitate tumor progression.

Antibodies, Monoclonal↗
PubMed1991

DNA binding of regulatory factors interacting with MHC-class-I gene enhancer correlates with MHC-class-I transcriptional level in class-I-defective cell lines.

Tumor cells frequently show a lack of surface class-I major histocompatibility complex (MHC) antigen expression. These molecules are key recognition structures for immune rejection of tumor cells and their absence at the surface of tumor cells could favor the progression of tumors. We have analyzed the transcriptional mechanisms that could lead to suppression of MHC-class-I expression in human tumor cell K562. The expression of MHC-class-I genes is highly controlled by regulatory factors interacting with an enhancer sequence upstream of MHC-class-I genes. In this report we show that DNA binding activity of 2 regulatory factors, KBFI and NF-kappa B, known to be essential for constitutive expression of MHC-class-I genes, is deficient in nuclear extracts from K562 cells. Induction of class-I gene expression at the surface of tumor cells by interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) shows that TNF-alpha can act in synergy with IFN-gamma to induce DNA binding of both factors NF-kappa B and KBFI to the class-I gene enhancer and that this induction of transcriptional factors is correlated with enhancement of MHC-class-I mRNA transcription and cell-surface antigen expression.

Antibodies, Monoclonal↗
PubMedDate not supplied

[Idiopathic hypereosinophilic syndrome: toward a new molecular-targeted therapy and a new cytomorphological and molecular definition].

Idiopathic hypereosinophilic syndrome is characterised by chronic hypereosinophilia leading to tissue damage, and after exclusion of reactive eosinophilia. Until recently no specific or efficient therapeutic was available. In 2003, a recurrent interstitial deletion 4q12 leading to the fusion of the FIP1L1 and PDGFRA genes was detected in hypereosinophilic syndromes. The resulting protein has constitutive tyrosine kinase activity which explains clinical and cytological remission of hypereosinophilic syndrome after treatment by a specific tyrosine kinase inhibitor, imatinib mesylate or Glivec, usually used in chronic myeloid leukaemia. Here we report a patient with hypereosinophilic syndrome associated to peculiar morphology of neutrophilic series and the 4q12 deletion. He presented clinical and haematological remission since the introduction of imatinib mesylate therapy.

Adult↗
PubMedDate not supplied

[Refractory anaemia with ringed sideroblasts (RARS) associated with marked thrombocytosis: a provisional entity in the WHO classification of haematological malignancies].

The WHO classification describes a group of myelodysplastic/myeloproliferative diseases, including a provisional entity, refractory anaemia with ringed sideroblasts (RARS) associated with marked thrombocytosis, underlining that is a provisional entity without consensus of belonging to myelodysplastic rather than to myeloproliferative syndromes. The authors report two cases with features of refractory anaemia with excess of ringed sideroblasts and marked thrombocytosis. In the first case, RARS is concomitant with thrombocytosis and fits the WHO criteria for this temporary entity. The second case is a typical RARS, who developed a thrombocytosis after several years and emphasizes that a link, at least progressive, exists between RARS and myeloproliferative disorders. The authors summed up the various situations related to secondary or primary acquired sideroblastic anaemia, likewise to primitive and reactive thrombocytosis. The cases of RARS + marked thrombocytosis reported in the literature are few in number and do not allow to settle between a particular form of myelodysplastic syndrome and a myeloproliferative disorder, a fully justified reason to classify these patients in a temporary group. To date, there is no codified therapy for this disorders.

Aged↗