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G Flandrin

Publications and source records attributed to G Flandrin.

At least 109 records · Page 6Linked to original sources
PubMed1989

Ph1-positive, bcr-negative acute leukemias: clustering of breakpoints on chromosome 22 in the 3' end of the BCR gene first intron.

About 50% of the Philadelphia-positive acute leukemias undergo molecular rearrangements outside the now classical bcr sequence (or M-BCR-1) rearranged in chronic myeloid leukemia (CML). Most of the breakpoints on chromosome 22 have been shown to be clustered in a 10.8-kb region of the first intron of the BCR gene (called bcr2 or m-BCR-1). In this report we examined two cases of Ph1 acute lymphoblastic leukemia in adult patients that exhibited breakpoints in a 5-kb segment of the BCR gene first intron, 16 kb upstream of the previously described cluster, suggesting the possibility of a second minor breakpoint cluster. In addition, the breakpoints on chromosome 9 were located in a region just 5' of the c-abl exon la.

Chromosomes, Human, Pair 22↗
PubMed1988

Cytogenetic study of 130 childhood acute nonlymphocytic leukemias.

Cytogenetic studies performed on 130 consecutive childhood acute nonlymphocytic leukemias (ANLL) investigated in the same center between 1977 and 1986 are reported. The incidence of clonal chromosomal abnormalities was 68.5% with uneven distribution among the groups of the FAB nomenclature. The high incidence of t(8;21) translocation cases, which was 58.6% of M2 ANLL cases, was remarkable. Complete remission rate was lower (P less than 0.05) in ANLL with all karyotypically abnormal metaphases (AA) than in the other ANLL (NN, with only normal metaphases, and AN, with a mixture of normal and abnormal metaphases). Median survival was also shorter in AA ANLL than in AN and NN cases (P less than 0.01). Median survival was different according to karyotype abnormalities: 11q anomalies and t(15;17) were not associated with a good prognosis, and the t(8;21) is not associated with a particularly long median survival (16 months) when compared with other ANLL as opposed to the results of others. The longest survival (26 months) was observed in patients with acute myelomonocytic leukemia with bone marrow eosinophilia. It may be concluded that chromosome studies have a prognostic value in childhood ANLL.

Bone Marrow Examination↗
PubMed1988

Cytogenetics of T-cell malignant lymphoma. Report of 17 cases and review of the chromosomal breakpoints.

Cytogenetic studies are reported on 17 T-cell malignant lymphomas (ML) including six cutaneous T-cell malignant lymphomas (CTCL). Due to the low incidence of rearrangements on bands where the T-cell receptor genes are located, other cases reported in the literature were analyzed in order to estimate the most frequent chromosomal breakpoints in ML, CTCL, and adult T-cell leukemia-lymphoma. Besides chromosomes 1 and 6q, 14q11, 7p15p21, and 7q32q35, the most frequent rearrangements involved bands 14q32, 2p11-p14, 2p23-p25, 17cen, 9p21p23, and 10p13p15. These results show that molecular studies must be concentrated on these chromosomal regions in order to identify the DNA sequences that may be involved in T-cell malignancies.

Adult↗
PubMed1988

Action of interferon-alpha on hairy cell leukemia: expression of specific receptors and (2'-5')oligo (A) synthetase in tumor cells from sensitive and resistant patients.

IFN-alpha induces tumor regression with a high percentage of complete remissions in hairy cell leukemia. We have recently reported that hairy cells express specific IFN-alpha receptors which are down-regulated upon therapy. We show here that the activity of 2-5 A synthetase, an IFN-induced enzyme, is 2 to 7-fold stimulated in hairy cells from responsive patients within 12-24 h after the first IFN dose. This in-vivo enzyme induction paralleled the kinetics of receptor down-regulation. In one patient who was unresponsive to IFN-alpha treatment neither expression of IFN-alpha receptor nor change in 2-5 A synthetase were expressed and modulated as in sensitive patients. In-vitro treatment of hairy cells with recombinant interferons showed that IFN-beta 1 was able to induce this enzyme to the same extent than IFN-alpha 2, whereas IFN-gamma was inactive despite the presence of specific IFN-gamma receptors. Our results indicate that IFN-alpha can exert its therapeutic effects by acting directly on the hairy cells through interaction with surface membrane receptors. Induction of 2-5 A synthetase can be one of the steps involved in this action. However, both mechanisms, as well as receptor down-regulation are not sufficient to explain the responsiveness of hairy cell leukemia to IFN-alpha.

2',5'-Oligoadenylate Synthetase↗
PubMed1988

[Perspectives for an epidemiological study of hairy cell leukemia].

A strong male predominance (4/1) has been noticed in all series of hairy cell leukemia (HCL) and we wonder whether there could be a link between male predominance and occupation. From a series of 161 patients observed by two different groups, the repartition of profession suggest an aetiological link between HCL and occupational exposure, particularly radiation, benzene and other solvents, since it appears that the proportion of medical workers (6%), mechanic divers (22%), printers and painters (10%) and farmers (11%) represent a high proportion of patients. Aware of the relative rarity of the disease we suggested to set up a national registry of the cases of HCL, the precise incidence of which remains unknown, and to start a classical case-referent study.

Female↗
PubMed1988

Molecular cloning of a 5' segment of the genomic phl gene defines a new breakpoint cluster region (bcr2) in Philadelphia-positive acute leukemias.

Molecular rearrangements of Ph1 chromosome, the hallmark of CML, are clustered in a 5.8-kb DNA segment, the so-called breakpoint cluster region (bcr) of the phl gene that is localized to chromosome 22q11. In Ph1-positive (Ph1+) ALLs, the rearrangements have been shown to involve either the 5.8-kb bcr (called bcr+) or a region upstream of bcr in the 5' end of the phl gene (bcr-). To gain insight into the rearrangements occurring in Ph1+ acute leukemias, a 64-kb DNA fragment from the 5' end of phl was analyzed in order to generate molecular probes covering 40 kb of the phl gene first intron. A panel of seven cases of bcr-Ph1+ acute leukemia (three nonlymphocytic and four lymphocytic) was investigated with these intron 1-derived probes. Strikingly, in six of the seven leukemias, the breakpoints were located in a 10.8-kb DNA segment, defining a new bcr which appears to be specific for Ph1+ acute leukemias. By analogy with the CML bcr region located in the 3' part of the phl gene, we propose to designate this 10.8-kb fragment bcr2.

Chromosome Mapping↗
PubMed1988

Philadelphia-positive acute leukemia: lineage promiscuity and inconsistently rearranged breakpoint cluster region.

Six patients with Philadelphia-positive (Ph1+) acute nonlymphocytic leukemia (ANLL) were studied by morphological, immunological, cytogenetic, and molecular techniques. Seven Ph1+ acute lymphocytic leukemia (ALL) cases were also studied for comparison. Three of ANLL cases were classified in M1, M2, and M4 groups of the FAB nomenclature, while the three other cases do not fit with any FAB subgroup and are described as M0. Immunophenotypical marker studies, double immunolabeling, and combined immunological and cytogenetic studies of metaphases showed that these ANLL expressed several lineage differentiation antigens. Rearrangements of immunoglobulin heavy chain gene (C mu) were detected in the six ANLL cases and in the seven ALL cases studied, as well as, in most cases, rearrangement of T cell receptor beta chain genes and/or T cell rearranging gamma genes. The results favored the assumption that the Ph1 translocation originated from a multipotent stem cell in Ph1+ ANLL. A common t(9;22) translocation was found in all cases, and additional chromosomal abnormalities were present in the six ANLL cases and in five of the seven ALL cases. Molecular studies of bcr gene configuration and c-abl transcription allowed two groups of Ph1+ ANLL to be distinguished. Three cases had bcr rearrangement and c-abl mRNA expression comparable to those reported in Ph1+ chronic myeloid leukemia, while three others had not detectable bcr rearrangement and a 7.2-7.5 kb c-abl mRNA. The existence of Ph1+ ALL with and without classical bcr rearrangement was confirmed.

Adolescent↗
PubMed1988

[The value of chromosome anomalies in the prognosis of acute non-lymphoblastic leukemia in children].

Cytogenetic studies performed on 130 consecutive childhood acute non lymphoblastic leukemias (ANLL) and investigated in the same center between 1977 and 1986 have been studied for their prognostic value. Clonal chromosome changes were detected in 68.5% (89/130) of the cases prior to treatment. Complete remission rate and median survival were significantly lower in patients with only abnormal metaphases than in patients with only normal metaphases (NN) or a mixture of normal and abnormal mitoses (AN). The ANLL with translocation t(8;21), which were 58.6% of the M2 ANLL, were not associated with a particularly long survival (16 months) when compared with AN and NN ANLL. The longest survival (26 months) was observed in patients with acute myelomonocytic leukemia with bone marrow eosinophilia. Cytogenetic analysis have a prognostic value in childhood ANLL.

Adolescent↗
PubMed1988

A primary immunoblastic T malignant lymphoma of the small bowel, with azurophilic intracytoplasmic granules. A histologic, immunologic, and electron microscopy study.

We report an aggressive primary T-immunoblastic lymphoma of the small intestine without blood involvement or associated celiac disease. Grossly, the tumor was composed of multiple disseminated ulcerated, infiltrating, or protuberant nodular lesions. Immunologic investigation showed that lymphoma cells were of peripheral (post-thymic) T-cell origin and expressed the phenotype associated with cytotoxic-suppressor subset (Leu4/CD3+, Leu9/CD7+, Leu2/CD8+, Leu11/CD16+, Leu 7/NKcells+, FcIgG+, HLA-DR+, anti-Tac/CD25+, Ki-1/CD30-, Leu1/CD5-, Leu5/CD2-, Leu3/CD4-). A particular morphologic feature of this case is the presence of numerous azurophilic granules within the lymphoma cells, identified as lysosomes by cytochemical and ultrastructural studies. In view of recent immunologic evidence that normal cytotoxic/suppressor T-cells selectively reside within the epithelium of the normal bowel and some of them contain azurophilic granules, it could be suggested that our patient's lymphoma represents a malignant counterpart of these lymphocytes. Furthermore, the aggressive character of this T malignant lymphoma (T-ML) could be related to the expression of T-cell activation markers HLA-DR and Tac/CD25 and the proliferation-associated antigen Ki-67 on a high proportion of tumor cells.

Cytoplasmic Granules↗
PubMed1987

Human T cell gamma genes are frequently rearranged in B-lineage acute lymphoblastic leukemias but not in chronic B cell proliferations.

T cell rearranging gene gamma (TRG gamma) and T cell antigen receptor beta (TCR beta) chain gene rearrangement and transcription were studied in a series of patients with B-lineage acute lymphoblastic leukemia (ALL), in which the Ig H chain genes are rearranged and the surface phenotype reproduces the stages of normal pre-B maturation. For comparison, polyclonal T cells from peripheral blood of healthy donors and blast cells from 19 cases of T lineage ALL were also studied. In this study we demonstrate the presence of a clonal rearrangement of the TRG gamma in 18 of the 22 B-lineage ALL cases and establish that this rearrangement, which generally involves the J gamma 1 region, is often monoallelic and appears different from the biallelic J gamma 2 rearrangement frequently seen in T-cell ALLs. In 9 of 22 cases, we found rearrangement of the genes of the TCR beta chain, which never involved the J beta 1 region. Conversely, the TRG gamma were seen in germline configuration in all 19 cases of B chronic lymphoid malignancies. In none of the 9 AML cases studied was TRG gamma and TCR beta chain gene rearrangement found. The TCR beta chain genes were rearranged in one B cell chronic lymphocytic leukemia (CLL). We also show that in B-lineage ALL, the cells probably use the same V gamma genes for TRG gamma rearrangements as the malignant cells in T-ALL and the polyclonal T cells. In none of the 13 B-lineage ALL cases investigated by Northern analysis was TCR beta mRNA expression detected, whereas a weak expression of TRG gamma transcripts was found in two of these cases. The correlations between surface phenotype, rearrangement of TRG gamma, TCR beta, and Ig H chain genes were analyzed. The significance of rearrangement of TRG gamma and TCR beta chain genes in B or pre-B cells is also discussed.

B-Lymphocytes↗
PubMed1987

Alpha-interferon in hairy cell leukaemia: direct effects on hairy cells or indirect cytotoxicity?

This report presents the results of a clinical trial on 53 patients with hairy cell leukaemia using low-dose alpha-interferon as therapy. Improvement of cytopenia and/or bone marrow hairy cell infiltration occurred in all but one patient. Often, blood and bone marrow improvements were dissociated and, after 7 or 13 months of therapy, complete remission was only observed in about 40% of patients. Recurrence of the disease was observed in some cases after cessation of therapy. A summary of the following results is presented: alpha-interferon receptor analysis, oncogene expression, study of the sensitivity of hairy cells to natural killer cells, and the effects of interferon on T-cell receptor gene rearrangement and on the function of T-cell clones. Results are also presented which show that myelofibrosis may be due to a release of platelet derived growth factor. The immunological findings and oncogene expression in 2 patients with a variant form of hairy cell leukaemia for which resistance to therapy was observed are also described. All the results show that interferon acts on hairy cells and are consistent with a direct effect by interferon in the treatment of hairy cell leukaemia.

Blood Platelets↗
PubMed1987

Cytogenetic studies on 519 consecutive de novo acute nonlymphocytic leukemias.

Cytogenetic studies were performed in the same laboratory on 519 untreated cases of de novo acute nonlymphocytic leukemia (ANLL) between 1977 and 1985. The overall incidence of clonal chromosome abnormalities was 54.3%; higher in children (67.5%) than in adults (50.4%). The distribution of chromosome abnormalities was uneven, according to the categories of the FAB nomenclature. The highest frequency of chromosome changes was observed in ANLL-M3 and the lowest in M1 and M6. The frequency of specific chromosome abnormalities and of their associated changes were also estimated. Monosomy 7 was detected in three patients with acute megakaryocytic leukemia (M7). Six cases with two abnormal chromosomally unrelated clones were observed and six constitutional chromosome abnormalities were detected. A clearer knowledge of the incidence of various chromosomal changes in ANLL seems necessary for better differentiation between the so-called primary and secondary chromosome abnormalities and for prognostic evaluation.

Acute Disease↗
PubMed1987

Trisomy 4: an entity within acute nonlymphocytic leukemia.

Trisomy 4 is a newly recognized primary chromosome change in leukemia. Five cases of acute nonlymphocytic leukemia (ANLL) are described from the United States and France. As in cases from Belgium, the only chromosome abnormality detected in the leukemic cells was trisomy 4. This was associated preferentially with ANLL of the M4 type (by FAB classification): acute myelomonocytic leukemia.

Acute Disease↗