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F Sigaux

Publications and source records attributed to F Sigaux.

At least 145 records · Page 8Linked to original sources
PubMed1987

[Rearrangement of the receptor genes of T cells for an antigen].

In this review, after a short description of the T-cell receptor alpha and beta gene organization, the results obtained by rearrangement analysis in human lymphoid proliferations are analysed. Southern analysis appear to be a useful tool for the study of clonality and at a less degree, of lineage involvement in such neoplasias. The significance of rearrangement of T-cell receptor genes in B-lineage proliferations is also discussed.

Cell Differentiation↗
PubMed1987

T cell rearranging gene gamma: diversity and mRNA expression in fresh cells from T cell acute lymphoblastic leukemia.

Rearrangement and in most cases expression of the T cell rearranging genes gamma (TRG gamma) and T cell antigen receptor beta chain (TCR beta) genes were studied in 19 cases of T cell acute malignancies where the surface phenotype is representative of the different stages of thymic maturation. TCR alpha gene transcription was also studied. TRG gamma and TCR beta genes were found to be rearranged in all but one case. The TRG gamma rearrangement pattern seen in most cases is compatible with biallelic rearrangement by loop excision involving the J gamma 2 regions. The sizes of all but two rearranged bands were identical to those of the rearranged bands seen in polyclonal T lymphocytes also studied in this work. One identical-sized band was found in 11 of the 18 rearranged cases. The expression of TRG gamma mRNA (transcripts of 1.6 kilobases [kb]) was highly variable from case to case and did not correlate with the stage of differentiation of the malignant cells, the expression of the molecules CD4 and CD8, the expression and size of the transcripts of the TCR beta genes, and the transcription of TCR alpha genes. In one CD3 + case, strong expression of the TRG gamma transcripts coexisted with the exclusive presence of TCR beta mRNA of 1.0 kb. The cells from this case did not react with anti-Ti antibody and exhibited no natural killer activity. These findings are suggestive of a malignancy that may express the recently isolated CD3-TRG gamma complex.

Acute Disease↗
PubMed1987

Splenectomy performed upon thirty-seven patients with hairy cell leukemia.

Thirty-seven patients with hairy cell leukemia underwent splenectomy. The postoperative course was uneventful for 34 patients. Improvement of peripheral cytopenia was obtained in the majority of patients. Survival time of patients who underwent splenectomy was significantly longer than for patients who did not undergo this procedure. Splenectomy is a habitually effective form of treatment for hairy cell leukemia, although not completely free of risks.

Adult↗
PubMed1987

Phenotypic and genotypic heterogeneity in large granular lymphocyte expansion.

The cellular heterogeneity of large granular lymphocyte expansions has been illustrated by the phenotypic and genotypic findings in five patients. In one patient whose circulating cells were CD2+, CD3-, CD5-, CD7+, CD8-, CD11+, Leu7+, CD16+, and displayed strong natural killer activity, no rearrangement of the T cell receptor beta-chain gene and T cell rearranging gene gamma was detected. The four other patients presented with neutropenia without overt lymphocytosis. In these patients the circulating lymphocytes expressed a predominant T cell phenotype CD2+, CD3+, CD5+, CD7+, CD8+, Leu7+. In three of them the presence of a T cell clone was demonstrated on the basis of a unique pattern of rearrangement of the T cell receptor beta-chain genes.

Aged↗
PubMed1987

Results of treating 53 hairy cell leukemia patients with alpha-interferon.

Fifty-three hairy cell leukemia patients were treated with low dose recombinant and natural alpha-interferon for 7 or 13 months with a marked improvement in peripheral blood and bone marrow findings. Our results suggest that daily injections have no advantage over three weekly injections, but longer treatment (12-13 months) is better than shorter treatment (6-7 months). The possibility of a relapse raises the issue of the place of splenectomy in the treatment strategy. Since the definition of remission and of relapse is based on the histological changes in the bone marrow, the necessity for the quantification of the hairy cell infiltration on bone marrow sections is stressed.

Dose-Response Relationship, Drug↗
PubMed1986

A t(8;14)(q24;q11) translocation in a T-cell leukemia (L1-ALL) with c-myc and TcR-alpha chain locus rearrangements.

Cell lines established from T-cell leukemias have recently been reported to exhibit a chromosome translocation t(8;14) involving proto-oncogene c-myc and the gene of the T-cell receptor alpha-chain(TcR-alpha). In this work, we have studied a case of T-cell leukemia presenting a t(8;14)(q24;q11) translocation that was found in fresh leukemic cells taken during relapse, but was absent in cells collected at diagnosis. Hybridization analysis showed that the breakpoint on chromosome 8 was located 3' to the c-myc exon 3. A TcR-alpha-specific original probe (D14S7, Mathieu-Mahul et al., 1985) revealed two differently rearranged patterns in DNA from leukemic cells obtained at diagnosis and during relapse. In contrast, the rearranged TcR-beta-gene DNA pattern did not change during the course of the disease, indicating that leukemic cells were clonally related. These data indicate that the chromosome breakpoint in 14q11 is situated in the TcR-alpha locus. These results suggest that translocations t(8;14) involving TcR-alpha and c-myc genes in T-cell malignancies are analogous to variant t(2;8) and t(8;22) translocations observed in Burkitt lymphoma. They also establish that the same types of molecular rearrangements due to a t(8;14)(q24;q11) translocation, at first described in T-cell lines established in culture, also exist in vivo and may play a role in the evolution of the leukemic process.

Child↗
PubMed1986

Interferon alpha in the treatment of hairy cell leukemia.

Fifty-four patients with hairy cell leukemia were treated for 7 months with three types of subcutaneously injected interferon: recombinant interferon alfa-2a from Hoffmann-La Roche (3 X 10(6) U daily); recombinant interferon alfa-2b from Schering (2 X 10(6) U/m2, three times per week); and partially purified human leukocyte interferon alpha from the Finnish Red Cross (3 X 10(6) U daily). After 4 months, in 27 patients hairy cells decreased dramatically (P less than 0.01) while platelets (P less than 0.05), monocytes (P less than 0.01), polymorphonuclear leukocytes (P less than 0.01) and hemoglobin (P less than 0.01) increased (in this order) as treatment progressed. Morphometric parameters were used to estimate the relative volume of hairy and myeloid cells present in bone marrow. Biopsies were performed at the beginning of the study and in the second, fourth, and seventh months thereafter. Bone marrow disorders were slower to improve as compared with blood. Six severe cases of hairy cell leukemia were responsive to treatment, but required special monitoring during the first 2 months. All three interferons studied are efficient. Interferon receptors, oncogene (mRNA levels) expression, and the relationship between PDGF and fibrosis in hairy cell leukemia are under investigation.

Adult↗
PubMed1986

Can peripheral T-cell lymphomas be morphologically subclassified? A morphometric approach to 21 cases.

Morphometric analysis of nuclear sizes and shapes was carried out on semithin sections of lymph node for 21 patients suffering from non-Hodgkin's peripheral T-cell malignant lymphoma (ML) (excluding mycosis and Sézary syndrome). Twenty cases of B-cell ML and three cases of Sézary syndrome with massive lymph node infiltration were also studied as references. Wright and Isaacson's recent proposals were applied to classify the peripheral T-cell MLs into monomorphic medium-cell ML (eight cases), pleomorphic ML (nine cases), and monomorphic large-cell ML (four cases). These three classes were readily distinguishable by morphometric analysis of nuclear sizes. Nuclear areas and their coefficients of variation were higher in pleomorphic MLs than in monomorphic medium-cell MLs (p less than 0.01). Large-cell monomorphic MLs were set apart by the histograms of their nuclear sizes. The mitoses were evaluated on histological sections and found to be more numerous in pleomorphic ML than in monomorphic medium-cell ML (p less than 0.05). Nuclear irregularity in the 21 cases of peripheral T-cell ML was lower than in Sézary cells. Morphometry clearly demonstrates the morphological distinctiveness of the subclasses of peripheral T-cell ML. Their biological significance has yet to be determined.

Adult↗
PubMed1986

Immunological typing of acute lymphoblastic leukemia: concurrent analysis by flow cytofluorometry and immunocytology.

For 60 cases of acute lymphoblastic leukemia (ALL) immunological typing was done concurrently by the avidin-biotin-peroxidase method using cytocentrifuged smears and by flow cytofluorometry for the study of surface antigens. The use of a large panel of antibodies detecting differentiation antigens allowed us to sub-classify 57/60 cases as 43 B-lineage ALLs and 14 T-lineage ALLs. The two types of ALL can be accurately distinguished by the expression of the antigens recognized by the antibodies of the clusters of differentiation CD19 (B4) and CD7 (Leu 9). Almost perfect agreement was obtained between the results of the two methods for antigens DR, CD10 (cALLA;J5) and CD7. A number of discordances were observed with other antigens [CD19 (B4), CD20 (B1), CD22 (To15), CD1 (T6), CD2 (T11), CD4 (T4), CD8 (T8), CD3 (T3), T9, T10]. In spite of these discordances, the avidin-biotin-peroxidase method can predict the lineage involved in most ALLs with a high degree of reliability. Nevertheless, for weakly expressed surface antigens (such as B4 and B1) the immunocytological method is less sensitive than flow cytofluorometry and can only approximately determine the stage of differentiation of neoplastic cells. Furthermore, the existence of cases which are at the same time negative with flow cytofluorometry and positive with immunocytology is consistent with the intracytoplasmic expression of certain differentiation antigens. Thus in the course of lymphoid differentiation, intra-cytoplasmic expression of T3, To15 and possibly J5 precedes their expression at the cell surface.

Antigens, Surface↗
PubMed1986

Treatment of hairy cell leukemia with recombinant alpha interferon: II. In vivo down-regulation of alpha interferon receptors on tumor cells.

Interferons (IFNs) initiate their effects by interacting with specific high-affinity cell surface receptors, but little is known about the physiology of IFN receptor interaction in vivo. Treatment of patients suffering from hairy cell leukemia (HCL) with human recombinant alpha IFN results in significant tumor regression, with clinical improvement in a high percentage of cases. To investigate a possible relevance of binding parameters as response markers, IFN receptor interaction on tumor cells responsive to IFN in vivo was studied. Binding of human alpha 2 IFN to circulating hairy cells was analyzed before and during IFN therapy in ten patients selected on the basis of high numbers of peripheral hairy cells. Binding experiments were carried out on Ficoll-Paque fractionated peripheral cell samples containing a majority of hairy cells. All patients reacted to recombinant alpha IFN treatment with a striking decrease in binding capacity within 12 hours after the first injection. As demonstrated by using a monoclonal antibody able to recognize alpha 2 IFN bound to its receptor, this decreased binding capacity was not due to blocking by circulating IFN but rather to a decrease in receptor number. This receptor "down-regulation" was partially reversible after the first IFN injection. However, upon prolonged IFN therapy, all patients displayed a stable state of decreased receptor expression. Down-regulation of IFN receptors can be regarded as a response marker to IFN treatment. This response marker, however, was not correlated with the clinical response within the first months of IFN therapy.

Animals↗
PubMed1986

[Translocation t(1; 14) and rearrangement of the gene for the alpha chain of the T-cell receptor in acute T-lymphoblastic leukemia].

A t(1; 14) (p32; q11) translocation has been found by the cytogenetic study of a T cell acute lymphoblastic leukemia patient. Molecular hybridization with a probe (D14S7) which recognizes a fragment of the alpha chain T receptor gene has shown a rearranged EcoRI 11.0 kb band in addition to the germline 3 and 8 kb bands. This translocation infrequently described until now is a new example of an alpha chain gene rearrangement in T cell malignancy. Moreover the breakpoint on chromosome 1 may also involve the newly isolated protooncogene, L-myc, normally localized on the chromosomal band 1 p32.

Adolescent↗
PubMed1986

c-myc and c-fos expression during interferon-alpha therapy for hairy cell leukemia.

Low-dose interferon-alpha (IFN-alpha) therapy is consistently effective in the treatment of hairy cell leukemia (HCL). In two cases of resistance to IFN-alpha administration, we diagnosed variant HCL, a form of HCL with intermediate features between typical HCL and B cell prolymphocytic leukemia. We tried to distinguish variant and typical hairy cells (HCs) by Northern blot analysis of the oncogenes expressed in vivo. We report that variant HCs contain c-myc transcripts in contrast to typical HCs, whereas c-fos transcripts are detected in both cell types. We also report that the mRNA levels of c-myc are not modified in variant HCs by IFN-alpha treatment, whereas the level of c-fos mRNA is modulated in both types of HCs. Our findings suggest that the failure to modulate c-myc expression in vivo might indicate the limits of low-dose IFN-alpha therapy.

Cell Cycle↗
PubMed1986

Treatment of hairy cell leukemia with recombinant alpha interferon: I. Quantitative study of bone marrow changes during the first months of treatment.

Seventeen patients with hairy cell leukemia (HCL) were treated with low doses of recombinant alpha interferon (IFN) for over 4 months. Marked improvement was observed in peripheral blood and bone marrow in 15 of 17 patients. Comparison of pretreatment values and hemograms obtained after 4 months of treatment showed a marked decrease in circulating hairy cells (P less than .01), a decrease in the number of lymphocytes (P less than .01), a rise in the number of platelets (P less than .05), granulocytes (P less than .05), and monocytes (P less than .01), and a rise in the hemoglobin level (P less than .01). Transient reduction in the number of granulocytes was noted during the first month. Correction of thrombocytopenia often appeared within 2 months and usually preceded improvement of anemia, monocytopenia, and neutropenia. Bone marrow biopsy specimens were taken before treatment and 2, 4, and 7 months after its initiation. The volumes occupied by hairy cells, cells of the myeloid lines, and adipocytes were studied by stereological analysis of semithin sections. Decrease in the volume occupied by hairy cells was seen after 4 months of treatment (P less than .01), and the volume continued to decrease at the seventh month (P less than .05). Hairy cells were no longer detected on bone marrow biopsies of 4 of 17 patients by the fourth month and in 3 of 8 additional patients by the seventh month. A rise in the volume occupied by normal myeloid cells was visible by the second month of treatment (P less than .01). Nevertheless, the volume occupied by granulocytes remained lower than in the normal controls (P less than .01). After an initial increase during the first 2 months of treatment (P less than .01), the overall cellularity remained unchanged at 4 months and decreased significantly (P less than .05) at 7 months. Except for biopsies at 2 months, mean cellularity was below that of control biopsies (P less than .01).

Biopsy↗
PubMed1985

Low-dose cytosine arabinoside treatment for acute nonlymphocytic leukemia in elderly patients.

Thirty patients older than 65 years of age with acute nonlymphocytic leukemia were treated with low-dose cytosine arabinoside (10 mg/m2 subcutaneously every 12 hours for 15 to 21 days). Fifteen achieved complete remission and five had partial remission. Treatment was more effective when initial bone marrow cellularity was low (P = 0.007). Four of six patients with secondary leukemia entered complete or partial remission. Therapy was well tolerated with reduced myelosuppression and few number of early deaths. Sixteen patients followed the whole treatment as outpatients. Six of 12 patients who achieved complete remission showed no evidence of post-therapeutic bone marrow aplasia. These data are consistent with the view that low-dose cytosine arabinoside acts on leukemic cells as a differentiating agent.

Acute Disease↗
PubMed1985

[Treatment of acute myeloblastic leukemia in elderly patients with low-dose cytosine arabinoside].

Forty-eight patients, aged from 65 to 88 years, presenting with de novo acute myelogenous leukemia were treated with a low-dose cytarabine regimen (10 mg/sq.m subcutaneously 12-hourly for 15 to 28 days). Twenty-four complete remissions and 7 partial remissions were obtained. The complete remission rate correlated with low initial bone marrow cellularity (p less than 0.05). Bleeding occurred in 28 patients and fever was noted, also in 28 patients. Four patients died of infection during induction treatment. Fourteen patients were treated as out-patients, but regular medical supervision was necessary. The median duration of complete remission was 8 months. The median survival for all patients was 15 months. It is concluded that low-dose cytarabine is an alternative to intensive chemotherapy in elderly patients with acute myelogenous leukemia.

Aged↗
PubMed1985

Two Burkitt's lymphomas with chromosome 6 long arm deletions.

Two new European Burkitt's lymphoma (BL) cases are reported. Their karyotypic abnormalities were unusual, without involvement of chromosomes #8, #14, #2, or #22. However, in both tumors, a 6q- chromosome was, present. These findings raise questions about the definition of BL and the involvement of various different DNA sequences in the mechanisms of BL genesis.

Adult↗