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F Valensi

Publications and source records attributed to F Valensi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Virological and molecular characterisation of a new B lymphoid cell line, established from an AIDS patient with primary effusion lymphoma, harbouring both KSHV/HHV8 and EBV viruses.

We report here a new case of primary effusion lymphoma (PEL), occurring in a French homosexual HIV-1 infected male with a pericardial, pleural and mesenteric tumour dissemination, and the establishment from his pleural effusion of a new cell line, Cra-BCBL, dually infected by EBV and KSHV/HHV8. Cra-BCBL cells are of B-cell origin as judged by their clonal immunoglobulin heavy chain (IgH) gene rearrangement, identical to that of the parental tumour. Both the cell line and the lymphoma cells expressed CD38 and CD45 antigens but no classical B-cell or T-cell lineage-restricted antigens. Cra-BCBL harbours a type I EBV virus, expressing a latency type II. Expression of KSHV/HHV8 ORF72 and ORF75 was detected by RT/PCR. In addition, KSHV lytic replication could be induced by treatment by n-butyrate. An equivalent and high copy number of KSHV genomes (20 to 200 copies by cell) was detected both in the primary tumour cells and in the cell line. Southern blot (SB) analysis of EBV terminal repeats (TR) displayed the same unique band in the cell line DNA and in the original tumour cells, consistent with a monoclonal infection of EBV. Furthermore, SB analysis of KSHV/HHV8 TR revealed the same hybridisation pattern between Cra-BCBL and the effusion cells, with a common band at around 30-40 kb corresponding to the fused termini of the viral episomes and a 5 Kb rearranged fragment. The new cell line characterised here could be a useful model to study interactions between two human herpes viruses and their contribution to lymphomagenesis.

Adult↗
PubMed1999

Persistent polyclonal B lymphocytosis with binucleated lymphocytes: a study of 25 cases. Groupe Français d'Hématologie Cellulaire.

Persistent and polyclonal lymphocytosis of B lymphocytes (PPBL) with binucleated lymphocytes is an entity characterized by a polyclonal lymphocytosis. The lymphocytosis is stable for years and binucleated lymphocytes are detected on peripheral blood smears. We previously described +i(3q) as a recurrent chromosomal abnormality in seven PPBL patients. In this study we report a large series of 25 PPBL patients and demonstrated that PPBL was associated with +i(3q) in 77% of cases, premature chromosome condensation (PCC) in 50% and both abnormalities in 41% of cases. Furthermore, we demonstrated that i(3q) was present in a minority of B cells, restricted to B lymphocytes independently of the kappa or lambda light Ig chain expression, and exclusively observed in non-binucleated cells. The benign clinical course of PPBL and the lack of biological evolution in the majority of cases suggest that recognition of these disorders is so important that aggressive therapy in PPBL has to be avoided. Whether this syndrome represents a premalignant or benign disease remains unclear. The persistence of cytogenetic abnormalities after stopping tobacco use suggests no association with cigarette smoking.

Adult↗
PubMed1999

NG2 expression in MLL rearranged acute myeloid leukaemia is restricted to monoblastic cases.

Expression of NG2 has been reported in the majority of paediatric acute leukaemia (AL) cases with MLL rearrangement. We demonstrated 7. 1 positivity in 2/3 paediatric and 4/11 adult MLL rearranged acute myeloid leukaemia (AML) but in 0/28 adult AML without MLL rearrangement, thus extending the 100% specificity to adult cases. Positivity correlated with stage of maturation arrest since it was found in 0/6 immature AML but in 6/8 monoblastic cases. These data demonstrate that, if NG2 expression in AL is the (in)direct result of MLL rearrangement, such activation is restricted to a monoblastic population in AML. They also have practical implications for NG2 diagnostic screening strategies.

Acute Disease↗
PubMed1998

Severe aplastic anemia of neonatal onset: a single-center retrospective study of six children.

We report severe aplastic anemia of neonatal onset diagnosed in six girls between 1985 and 1995 in a single center. Initial blood cell counts (mean age 3.8 days old, 1 to 15 days) showed thrombocytopenia (six of six), anemia (four of six), and neutropenia (two of six). Neutrophil counts gradually decreased below 0.5 x 10(9)/L, and severe aplastic anemia occurred in three patients by 3 months of age and in all patients by 1 year of age. Lymphocyte number and functions were normal. In all children bone marrow biopsy showed hypocellularity for age and absence of fibrosis, blasts, lymphocytic infiltrates, and cytologic abnormalities. Blood and medullary cytogenetic studies were normal. A search for known constitutional, viral, or toxic causes was negative. Immunosuppressive therapy failed to restore hematopoiesis (three of six). Five children received a bone marrow transplantation at an average age of 9 months (range 2.7 to 29 months). One child is alive and well after a human leukocyte antigen-identical bone marrow transplantation, whereas the other four died. Both congenital onset and the high rate of familial involvement suggest that this condition may be inherited.

Anemia, Aplastic↗
PubMed1998

Quantitative RNA slot-blot analysis of CCND1/cyclin D1 expression in suspected mantle cell lymphoma.

Abnormal CCND1 expression is found in the majority of mantle cell lymphomas (MCL) and in a minority of other mature B cell malignancies. Its evaluation can therefore aid diagnostic classification, in conjunction with clinical, morphological, immunophenotypic and cytogenetic analysis. We describe a rapid slot-blot hybridization technique allowing quantitative assessment of CCND1 expression relative to beta-actin, with a sensitivity cut-off of approximately 10%. This allowed clear separation (P < 0.01) of CCND1 MCL (0.89 +/- 0.4; range 0.23-1.81; n = 25) from control samples (0.02 +/- 0.04; range 0-0.09; n = 22) on limited quantities of RNA (1-3.5 microg). Of nine samples in which a potential diagnosis of MCL lymphoma was based on morphological analysis of paraffin-embedded material, without adequate immunophenotype analysis, all were CCND1 negative and subsequent immunophenotype demonstrated features compatible with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) (CD5+, CD23+, FMC7-) in all cases tested. This study demonstrates the feasibility of slot-blot CCND1 quantification and the importance of the availability of cryopreserved material.

Adult↗
PubMed1998

Cutaneous T cell lymphomas: mycosis fungoides, Sezary syndrome and HTLV-I-associated adult T cell leukemia (ATL) in Mali, West Africa: a clinical, pathological and immunovirological study of 14 cases and a review of the African ATL cases.

Cutaneous T cell lymphomas (CTCL) are rare lymphoproliferative diseases, which are frequently suspected to be of viral origin. As very few data were available concerning cutaneous T cell lymphomas in tropical Africa, we undertook a clinical, histopathological, immunological and viro-molecular study of patients with a clinical diagnosis of cutaneous lymphoma, in Bamako, Mali. While prior to this study, no case of CTCL had been reported in this country, 14 patients (five women, nine men; mean age 58 years) with a diagnosis of cutaneous lymphoma were seen over a period of 30 months (1992-1994) in the only dermatological department in Mali. Clinically, the most frequent pattern was an infiltrated erythrodermia similar to Sezary syndrome. Nodular lesions and/or plaques were rarely observed. All these cutaneous tumors were T cell lymphoproliferations, only one expressing the CD8+ antigen. A comprehensive analysis of all the available data permitted characterization of three cases of adult T cell leukemia/lymphoma (ATL) associated with HTLV-I (one definitive case, of leukemic type, with demonstration of clonal integration of HTLV-I proviral genome and two probable ATL cases), three cases of Sezary syndrome (SS), two cases of mycosis fungoides (MF) and five cases of pleomorphic cutaneous lymphoma. In one case, the differentiation between MF and pleomorphic cutaneous lymphoma could not be established. HTLV-I serological and/or molecular markers were restricted to the three ATL cases. From the unique definitive ATL case, a T cell line was established from culture of peripheral blood mononuclear cells and sequence analysis of the env gene and the U3-LTR region demonstrated that the virus present in this patient belonged to the cosmopolitan subtype A. Thus, we report here the first evidence of HTLV-I infection and associated ATL in Mali. This is the second ATL case described for the whole Sahelian region (one ATL of the lymphoma type was reported previously in a Mauritanian patient). Furthermore, we demonstrate that the main types of CTCL described in Europe and North America are also present in this African area and that the prevalence of these diseases is greatly underestimated in such regions. Furthermore, no association was observed between HTLV-I/II infection and SS, MF or pleomorphic cutaneous lymphoma in Mali in contrast to other studies.

Adult↗
PubMed1998

Genetic analysis of splenic lymphoma with villous lymphocytes: a Groupe Français d'Hématologie Cellulaire (GFHC) study.

In order to characterize the genetic diversity in splenic lymphoma with villous lymphocytes (SLVL), we have undertaken cytogenetic and molecular analyses of CCND1 expression and BCL1-IgH PCR rearrangement in 76 cases diagnosed predominantly on morphological criteria. Cytogenetic abnormalities were detected in 19/44 (43%) of cases, including in 16/25 (64%) of cases with an absolute lymphocytosis. Abnormalities included those involving chromosome 14q32 (9/19, 47%), predominantly t(11;14)(q13;q32) (5/19, 26%), chromosome 3 (26%), predominantly 3q, chromosome 17p (26%) and trisomy 12 (3/19, 16%) and were thus suggestive of pathogenetic diversity. CCND1 was expressed in 8/30 (27%) cases, including in all t(11;14) cases, 5/10 (50%) CD5-positive cases and also in 3/20 (15%) CD5-negative cases. Three CCND1-positive SLVL demonstrated immunophenotypic features similar to mantle cell lymphoma (MCL) but the majority differed in their CD5 negativity or CD23 positivity. BCL1-IgH rearrangement was only seen in 1/62 (2%) of cases overall and in none of the t(11;14) cases, which demonstrated FISH breakpoints both centromeric and telomeric to the BCL1/MTC, suggesting that, if genomic clustering exists in t(11;14) SLVL, it differs from MCL. Although CCND1 expressing SLVL more commonly had marked lymphocytosis, they did not demonstrate a more aggressive clinical course than their negative counterparts, demonstrating that the detection of CCND1 expression or of a t(11;14) should not suffice to alter diagnostic classification in the absence of other criteria.

Aged↗
PubMed1998

TAL1 expression does not occur in the majority of T-ALL blasts.

The TAL1 gene is disrupted by translocation or deletion (tal(d)) in up to 30% of T-cell acute lymphoblastic leukaemia (T-ALL), leading to aberrant transcriptional activation, as a SIL-TAL1 fused transcript in tal(d). It has been suggested that TAL1 transcription occurs in approximately 50% of a T-ALLs without apparent rearrangement. SIL-TAL1 was positive in 15/60 (25%) of T-ALL, whereas wild-type TAL1 transcripts were detected in all 13 SIL-TAL1 and in 19/43 (44%) T-ALL without SIL-TAL1. To investigate the cellular origin of TAL1 we exploited the fact that GATA1 and TAL1 are co-ordinately expressed in non-lymphoid haemopoietic cells, whereas only the latter is found in T-ALL. GATA1 was detected in 10/23 (43%) TAL1-negative T-ALLs but in 17/19 (89%) 'unexplained' TAL1-positive cases, suggesting a common non-lymphoid cellular origin. Immunocytochemical analysis with a TAL1-specific monoclonal antibody showed nuclear expression in the blasts of 10/34 (29%) cases, including 8/10 SIL-TAL1+ and two RT-PCR TAL1+, SIL-TAL1- cases. In the remaining cases TAL1 expression was restricted to a minor population (< 5%) of larger, strongly TAL1-positive cells which comprised erythroid cells, CD34+ CD3- precursors and an unidentified TAL1+ CD45- population which morphologically resembled monocytes/macrophages. We therefore suggest that appropriate diagnostic evaluation of T-ALL should include molecular detection of SIL-TAL1 transcripts and in situ immunocytochemical detection of TAL1 protein expression by leukaemic blasts. This approach will enable accurate analysis of the prognostic significance of TAL1 deregulation in T-ALL.

Adolescent↗
PubMed1998

FISH detection of chromosome 14q32/IgH translocations: evaluation in follicular lymphoma.

A FISH strategy capable of detecting chromosome 14q32 rearrangements involving the IgH locus, including in interphase nuclei, was developed using Ig variable and constant region cosmids from the extremities of the locus in a dual hybridization approach, using signal splitting as evidence of rearrangement. The large size of the locus (1.3 Mb) and the propensity for internal deletion due to physiological VDJ recombination and isotype switching complicate analysis of this locus. We used the Ig10 cosmid, which hybridizes to C epsilon and C alpha2 at the 3' end of the constant region, in order to minimize deletion and/or splitting of the constant region probe. Cos Ig10 and the IgV18 VH probes were compared with a specific IgH-BCL2 FISH dual hybridization approach in follicular lymphoma (FL). Both were capable of detecting the t(14;18) in interphase nuclei, including in cases with no apparent abnormality by classic karyotype analysis, although the sensitivity of the IgH approach was slightly lower. We have also successfully applied these probes to whole cell cytospin preparations, rendering analysis of cryopreserved material possible, although interpretation should be limited to frequent events, particularly following cell manipulation. Analysis of flow cytometric sorted bone marrow fractions from three FL patients by FISH and FICTION showed that the t(14;18) was present in a much lower proportion of CD34 positive than negative cells but that the higher level of background hybridization limits use of these techniques for the reliable quantification of rare events.

Cell Separation↗
PubMed1997

[Polyclonal lymphocytosis with binucleated lymphocytes. Morphological, immunological, cytogenetic and molecular analysis in 15 cases].

OBJECTIVES: Describe the clinical, immunological, cytogenetic and molecular aspects of polyclonal lymphocytosis with binucleated peripheral lymphocytes in order to ascertain the therapeutic consequences. PATIENTS AND METHODS: Fifteen patients, 13 women, 2 men, with a total lymphocyte count persistently above 4 x 10(9)/l at successive counts and binucleated lymphocytes on blood smears were studied. RESULTS: The syndrome is easily recognized at careful examination of blood smears which show binucleated lymphocytes and lymphoid cells with heterogeneous morphology. The lymphocytosis is polyclonal. The clinical situation remains stable without treatment despite cytogenetic clonality which contrasts with molecular polyclonality. DISCUSSION: Polyclonal lymphocytosis with binucleated lymphocytes is a clinical entity characterized by 1) nearly exclusive female predominance, mainly in young smokers; 2) lymphocyte counts above 4 x 10(9)/l which persist (> 6 months), are unchanged over time and fortuitously discovered; 3) lymphocytosis with binucleated lymphocytes on blood smears; 4) polyclonal lymphocytosis; 5) increased polyclonal serum IgM; and 6) recurrent cytogenetic anomalies with an isochromosome supenumerary marker, e.g. +i (3q). The etiology remains unknown: the role of smoking genetic predisposition or viral factors remains to be determined.

Adult↗
PubMed1997

Human herpes virus 8 (Kaposi's sarcoma herpes virus) and malignant lymphoproliferations in France: a molecular study of 250 cases including two AIDS-associated body cavity based lymphomas.

The new human herpes virus 8 (HHV8) was recently detected in cases of body cavity based lymphoma (BCBL), a rare B cell lymphoma, mostly AIDS-associated. We investigated for HHV8 DNA sequences a series of 250 B or T cell lymphoproliferative malignancies, as seen in France, including 126 leukemias and 124 lymphomas (232 non-AIDS-associated and 18 AIDS-associated tumors). HHV8 sequences were detected in only three patients. The first two were homosexual males, HIV-infected since 1985 who suffered from a BCBL initially characterized in one case by a pleural lymphomatous effusion and a peritoneal one in the other case. A high level of HHV8 copies was detected in the tumoral cells of these two BCBL. In contrast, in the third positive patient who had an AIDS-associated immunoblastic lymphoma, the HHV8 sequences level was quite low. In the two BCBL patients, the HHV8-infected clonal B cells had a large immunoblastic feature with an indeterminate phenotype and were also infected by Epstein-Barr virus. In one BCBL case, a semiquantitative PCR analysis revealed that the HHV8 sequences were much more abundant in the effusion tumor cells than in the cutaneous Kaposi's biopsy while no HHV8 sequence was detectable in the peripheral blood lymphocytes. This study reports HHV8-associated BCBL in European AIDS patients and confirms that HHV8 is present at a high copy number in the tumoral B cells of this malignancy. Furthermore, HHV8 does not seem to play a pathogenic role in any of the other T or B malignant lymphoid neoplasias studied so far. This study also stresses the necessity for quantification studies in interpretation of a positive PCR analysis for HHV8 sequences, especially in patients at risk for HIV infection or Kaposi's sarcoma.

Adult↗
PubMed1997

Alternative origin of p13MTCP1-encoding transcripts in mature T-cell proliferations with t(X;14) translocations.

The MTCP1 gene is involved in the t(X;14)(q28;q11) translocation associated with T-cell prolymphocytic leukemia and related conditions. This gene is unusual in that it codes for two distinct proteins: a small mitochondrial protein, p8MTCP1, and a putative oncogenic protein, p13MTCP1. Scarcity of material from t(X;14)-associated proliferations and very low levels of mRNA expression have so far prevented a thorough description of p13MTCP1-encoding transcripts. Here, we characterize two additional t(X;14) bearing leukemias allowing this analysis. In one case, with a breakpoint located 5' to the MTCP1 gene, the level of transcription of previously described p13MTCP1-encoding transcripts is enhanced. In the second case, with a breakpoint within the MTCP1 intron I, an alternative transcription initiation site is demonstrated in the tumor cells at 229 bp upstream to exon II. The identification of this internal promoter, together with the similarity between TCL1 and MTCP1 genomic structures, allow us to propose a model in which the duplication of an ancestral gene was followed by the insertion of one copy within the intron of a p8-encoding gene, accounting for the unusual feature of the MTCP1 gene.

Aged↗
PubMed1997

The majority of myeloid-antigen-positive (My+) childhood B-cell precursor acute lymphoblastic leukaemias express TEL-AML1 fusion transcripts.

The t(12:21) translocation fuses the TEL and AML1 genes and has been found in up to 28% of paediatric B-cell precursor acute lymphoblastic leukaemias (BCP-ALL). The AML1 gene is a transcription factor which regulates expression of several myeloid differentiation associated genes. A molecular analysis of TEL-AML1, E2A-PBX1, MLL-AF4, BCR-ABL expression and an immunophenotypic study of CD13/CD33 myeloid antigen expression have been performed prospectively on tumour cells from 96 paediatric BCP-ALL patients. Percentages of CD13 or CD33 expressing leukaemic cells were found to be higher in TEL-AML1 positive cases (n = 22) than in TEL-AML1 negative (n = 74) cases (P<0.001). In 22/96 cases (23%) >10% of neoplastic cells were found to express at least one of the two markers. In 14 of these cases (63%), TEL-AML1 expression was detected, whereas t(4;11), t(11;19) and t(9;22) translocations were found by molecular methods in only three cases (14%). In four cases (18%) no molecular marker was found. These data show that TEL-AML1 expression is significantly associated with myeloid antigen expression by leukaemic cells and suggests that the prognostic significance of myeloid antigen expression in paediatric ALLs should be re-evaluated in the light of molecular cytogenetic markers.

Antigens, Differentiation, Myelomonocytic↗
PubMed1997

Simultaneous SIL-TAL1 RT-PCR detection of all tal(d) deletions and identification of novel tal(d) variants.

Site-specific deletions of the 5' part of the TAL1 gene (tal(d)) are among the most frequent non-random genetic abnormalities in T-cell acute lymphoblastic leukaemia (T-ALL). They are usually detected by PCR from DNA with several primer pairs or by Southern blot analysis. Since tal(d) lead to expression of a SIL-TAL1 fusion transcript, irrespective of the genomic breakpoint, we have used a single monoplex RT-PCR reaction to screen 55 T-ALL patients at diagnosis. SIL-TAL1 transcripts were demonstrated in 12 (22%) cases, including 7/27 (26%) children <15 years of age, 2/8 (25%) adolescents and 2/17 (12%) adults aged >20 years. SIL-TAL1 RT-PCR was preferrable to tal(d) DNA PCR since it allowed the simultaneous detection of tal(d), tal(d2) and two previously undescribed tal(d) variants. SIL-TAL1 RT-PCR screening should therefore increase the detection rate of tal(d) by approximately 15-20%, with an at least comparable sensitivity to tal(d) genomic PCR, and represents a more practical and economic alternative to multiple DNA PCRs or Southern blotting when incorporated into molecular screening for multiple transcripts at diagnosis.

Adolescent↗
PubMed1996

Expression of p13MTCP1 is restricted to mature T-cell proliferations with t(X;14) translocations.

T-cell prolymphocytic leukemia (T-PLL), a rare form of mature T-cell leukemias, and ataxia telangiectasia clonal proliferation, a related condition occurring in patients suffering from ataxia telangiectasia, have been associated to translocations involving the 14q32.1 or Xq28 regions, where are located the TCL1 and MTCP1 putative oncogenes, respectively. The MTCP1 gene is involved in the t(X;14)(q28;q11) translocation associated with these T-cell proliferations. Alternative splicing generates type A and B transcripts that potentially encode two entirely distinct proteins; type A transcripts code for a small mitochondrial protein, p8MTCP1, and type B transcripts, containing an additional open reading frame, may code for 107 amino-acid protein, p13MTCP1. The recently cloned TCL1 gene, also involved in translocations and inversions associated with T-cell proliferations, codes for a 14-kD protein that displays significant homology with p13MTCP1. We have generated rabbit antisera against this putative p13MTCP1 protein and screened for expression of p13MTCP1 normal lymphoid tissues and 33 cases of immature and mature lymphoid T-cell proliferations using a sensitive Western blot assay. We also investigated the MTCP1 locus configuration by Southern blot analysis. The p13MTCP1 protein was detected in the three T-cell proliferations with MTCP1 rearrangements because of t(X;14) translocations, but neither in normal resting and activated lymphocytes nor in the other T-cell leukemias. Our data support the hypothesis that p13MTCP1 and p14TCL1 form a new protein family that plays a key role in the pathogenesis of T-PLL and related conditions.

Amino Acid Sequence↗
PubMed1996

Cytokine response of B lymphocytes from splenic lymphoma with villous lymphocytes: correlation with TNF-RII (p75) and CD11c expression.

We studied the immunophenotype and the functional reactivity to cytokines of blood cells from eight patients with Splenic Lymphoma with Villous Lymphocytes (SLVL). Cells from all cases exhibited moderate to high levels of membrane immunoglobulin, CD22 and CD40 antigens and light chain restriction (kappa/lambda: 1.7/1). CD44, CD54 and CD11b expression was detected in all cases whereas CD11c was expressed in only four cases (50%). CD11c+ cells lacked CD21 and CD23 expression whereas CD11c cells expressed both these antigens. Cells from most patients (7/8) responded to IL2 whereas only four responded to IL4 and three to TNF alpha. The response to TNF alpha correlated with spontaneous TNF-RII and CD11c expression. Although two days of culture induced the TNF-RII expression in CD11c cells, they remained unresponsive to TNF alpha. These two groups of SLVL patients also differed by IL10 mRNA content: the former (CD11c+, TNF-RII+) contained TNF alpha and IL10 mRNA whereas the latter (CD11c, TNF-RII) lacked IL10 mRNA, even after two days of culture. There were thus two groups of SLVL patients: CD11c+ and CD11c, exhibiting different patterns of cytokine response and production. These groups may correspond to different cell origins or different progression stages of the disease.

Aged↗