Biomedical subjects

L Michaux

Publications and source records attributed to L Michaux.

At least 37 records · Page 2Linked to original sources

PubMed2001

Complex karyotype and absence of mutation in the c-kit receptor in aggressive mastocytosis presenting with pelvic osteolysis, eosinophilia and brain damage.

Aggressive mastocytosis is a form of systemic mast cell disease (SMCD) characterized by organ infiltration, bone lesions. eosinophilia and lymphadenopathies. Here we report a patient with unusual clinical features, namely osteolysis without other bone lesions commonly found in SMCD, major eosinophilia and cerebral infarction. The mast cells exhibited a classical immunophenotype (CD2+, CD9+, CD13+, CD25+, CD35+, CD45c+ and CD117+). Cytogenetic investigation showed novel complex aberrations, and clonal evolution was correlated with clinical progression. The screening for recurrent point mutations affecting the c-kit gene was negative. Mainly, the ASP816VAL substitution was not detected in our patient. Treatment with steroids and interferon was only temporarily effective.

Aged↗

PubMed2001

Atypical lymphocytic leukemia and mantle cell lymphoma immunologically very close: flow cytometric distinction by the use of CD20 and CD54 expression.

Integration of morphological and immunophenotypic data is critical in achieving diagnosis accuracy and minimising interobserver interpretative discrepancies. The aim of this work was to compare the immunophenotype and the morphology of chronic lymphocytic leukaemia and mantle cell lymphoma, to help in the differential diagnosis of CD5 positive monoclonal B cells. Frozen/thawed samples from 91 patients were analysed retrospectively. Fresh samples from 17 mixed/atypical CLL and 13 MCL were tested to corroborate the results. Markers were analysed as percentage (%) of positive B lymphocyte subpopulation, and in terms of median fluorescence intensity (MFI). Matutes's CLL score clearly allowed distinguishing between classical CLL on the one hand, and atypical CLL and MCL on the other hand. The percentage of CD54-positive cells and the median fluorescence intensity of CD20 and CD54 were the only parameters which were significantly higher in MCL than in atypical CLL (P < 0.05), allowing an immunological distinction between these two entities. Nevertheless, due to a quenching problem when using CD20 and CD54 together, and because CD18 showed a statistically different expression between classical and atypical CLL, the combination of CD18/CD54 has been preferred and showed a different pattern in the three entities. Immunophenotyping could be helpful in the differential diagnosis of CD5-positive B cell chronic lymphoproliferative disorders with atypical features that do not fit exactly into any of the morphologic proposed groups.

Adult↗

PubMed2001

Second primary tumors and immune phenomena after fludarabine or 2-chloro-2'-deoxyadenosine treatment.

The purine nucleoside analogs fludarabine and 2-chloro-2'-deoxyadenosine display substantial activity in the treatment of various chronic lymphoproliferative disorders. Their major toxicities are primarily immunosuppression and myelosuppression. The profound influence of these drugs on the immune system has raised questions as to the emergence of secondary neoplasms or auto-immune disorders after their use. Based on a literature review and on personal observations, this article reviews the potential clinical importance of these concerns.

Antineoplastic Agents↗

PubMed2000

Analysis of the P53, RB/D13S25, and P16 tumor suppressor genes in marginal zone B-cell lymphoma: An interphase fluorescence in situ hybridization study.

The genetic mechanisms underlying the genesis, disease progression, and high-grade transformation of marginal zone B-cell lymphoma (MZBCL) are poorly understood. We analyzed 33 cases of histologically and immunophenotypically well-characterized MZBCL (12 extranodal, 11 nodal, and 10 splenic MZBCL; 27 at primary diagnosis and six during the course of disease) by dual-color interphase fluorescence in situ hybridization (FISH) for deletions of tumor suppressor genes. We investigated loci known to play a role in the genesis or disease progression of other subtypes of lymphoid malignancies, namely the P53 gene (17p13), the retinoblastoma gene (RB, 13q14), the D13S25 locus (13q14), and the P16(INK4A) gene (9p21). Heterozygous deletions of P53 were detected in three out of the 33 cases, including two splenic and one extranodal MZBCL. One of these patients was analyzed at primary diagnosis and two during the course of disease. Heterozygous deletions of the RB gene (nodal MZBCL) and D13S25 (splenic MZBCL) were found in one case each. P16 deletions were not detected in any of our cases. We conclude that deletions of the analyzed tumor suppressor genes are relatively rare in MZBCL, which contrasts with the findings in some other subtypes of NHL.

Aged↗

PubMed2000

Chronic myeloid leukemia with a rare variant Philadelphia translocation: t(9;22;21)(q34;q11;q22).

A case of chronic myeloid leukemia displaying an uncommon t(21;22)(q22;q11) is reported. For the first time, this translocation has been characterized by fluorescence in situ hybridization (FISH) and the reverse transcriptase polymerase chain reaction (RT-PCR). FISH, with the use of whole-chromosome painting probes and probes specific for the BCR and ABL genes, showed a three-way variant Philadelphia translocation (9;22;21)(q34;q11;q22) with a BCR/ABL fusion residing on the der(22). In addition, RT-PCR demonstrated a b2a3 BCR/ABL fusion transcript. Underlying mechanisms and prognostic implications are discussed.

Chromosome Banding↗

PubMed2000

Genetic abnormalities in marginal zone B-cell lymphoma.

Marginal zone B-cell lymphoma (MZBCL) including extranodal mucosa-associated lymphoid tissue (MALT)-type lymphoma, nodal, and splenic MZBCL represents a distinct subtype of B-non-Hodgkin's lymphoma. Recently, important progress in the elucidation of the genetic mechanisms underlying the pathogenesis and disease progression of these lymphomas has been made. The API2 gene, an inhibitor of apoptosis, and the novel MLT gene have been found to be altered by the t(11;18)(q21;21), which represents the most frequent structural chromosomal abnormality in extranodal low-grade MALT lymphoma. Another gene involved in the regulation of apoptosis, the BCL10 gene, has been cloned from a MALT lymphoma cytogenetically characterized by the t(1;14)(p22;q32). Along the same lines, inactivating mutations of the proapoptotic FAS gene have been detected in a relatively high proportion of extranodal MZBCLs. Considering these data and the fact that at least some MALT lymphomas show low levels of apoptosis and seem to escape from FAS-mediated apoptosis one may speculate that abrogation of apoptosis constitutes a central pathogenetic mechanism in the development of these lymphomas. The pathogenetic role of trisomy 3, the most frequent numerical chromosomal change of MZBCL, is not known. The minimal overrepresented region has been delineated to 3q21-23 and 3q25-29 using comparative genomic hybridization. The BCL6 proto-oncogene, located on 3q27, which is rearranged in some MZBCL and a high proportion of large cell B-cell lymphomas with extranodal localization, represents one of the candidate genes residing in these critical regions.

Chromosome Aberrations↗

PubMed2000

MLL amplification in myeloid leukemias: A study of 14 cases with multiple copies of 11q23.

We here report the clinical, cytogenetic, fluorescence in situ hybridization (FISH), and Southern blot data on 14 patients with a myeloid malignancy and structural aberration of chromosome band 11q23 associated with overrepresentation or amplification of the MLL gene. The number of copies of MLL varied from three (two cases) to a cluster consisting of multiple hybridization spots. Together with previous reports, available data indicate that amplification of 11q23/MLL is a recurrent genetic change in myeloid malignancy. It affects mainly elderly patients and is often associated with dysplastic bone marrow changes or with complex karyotypic aberrations, suggestive of genotoxic exposure. It is associated with a poor prognosis. In addition, FISH analysis of nine cases with additional 11q probes showed that the overrepresented chromosomal region is generally not restricted to MLL, and Southern blot analysis indicated that amplification does not involve a rearranged copy of this gene. The significance of MLL amplification and the mechanisms by which it could play a role in leukemogenesis and/or disease progression remain to be elucidated.

Adult↗

PubMed2000

The value of interphase fluorescence in situ hybridization for the detection of translocation t(12;21) in childhood acute lymphoblastic leukemia.

Translocation t(12;21)(p13;q22) is the most frequent cytogenetic abnormality in childhood acute lymphoblastic leukemia (ALL) and is generally associated with favorable prognosis. In this report, we assessed the value of dual-color interphase fluorescence in situ hybridization (FISH) for the detection of t(12;21). Fifty-three patients were screened for ETV6/CBFA2 fusion by means of FISH, using two cosmid probes mapped on ETV6 and on CBFA2, respectively. The cut-off value (mean + three standard deviations) for positivity established on control patients was 9.3%. A comparison between FISH and molecular methods [reverse-transcriptase polymerase chain reaction/Southern blot (RT-PCR/SB)] was possible in 52 patients: 34 of 52 (65.4%) showed negative results with both approaches, and 13 of 52 (25%) were positive; 5 of 52 (9.6%) showed discrepancies: four patients who were positive using RT-PCR/SB were negative using FISH. Conversely, one patient negative when using RT-PCR/SB was positive with FISH. Further investigations on this patients, cytogenetically characterized by add(12p), showed an atypical breakpoint on ETV6, located 5' to the common breakpoint. Compared with RT-PCR and SB, dual-color interphase FISH with the cosmid probe set proved to be highly specific but showed limited sensitivity.

Blotting, Southern↗

PubMed2000

Polysomy 13 with concomitant deletion of 13q13-14 involving the retinoblastoma gene and the D13S25 locus in a case of acute myeloid leukemia.

We herein describe a case of acute myeloblastic leukemia (AML), FAB subtype M4, with an unfavorable clinical course and a complex karyotype, including 4-9 copies of chromosome 13. Polysomy 13 was a result of clonal evolution. Fluorescence in situ hybridization (FISH) revealed a cytogenetically unrecognizable deletion within 13q13-14 that included the retinoblastoma gene (RB) and the D13S25 locus in all but one copy of chromosome 13. The only chromosome 13 that did not show a deletion affecting the q13-14 region was translocated to chromosome 7, resulting in a dic(7;13)(q21;p11). In this case, the coexistence of polysomy and a partial deletion within the same chromosome point toward a possible formation of a fusion product with oncogenic potential and its consecutive amplification as a critical alteration in this case.

Aged↗

PubMed2000

IL-TIF/IL-22: genomic organization and mapping of the human and mouse genes.

IL-TIF is a new cytokine originally identified as a gene induced by IL-9 in murine T lymphocytes, and showing 22% amino acid identity with IL-10. Here, we report the sequence and organization of the mouse and human IL-TIF genes, which both consist of 6 exons spreading over approximately 6 Kb. The IL-TIF gene is a single copy gene in humans, and is located on chromosome 12q15, at 90 Kb from the IFN gamma gene, and at 27 Kb from the AK155 gene, which codes for another IL-10-related cytokine. In the mouse, the IL-TIF gene is located on chromosome 10, also in the same region as the IFN gamma gene. Although it is a single copy gene in BALB/c and DBA/2 mice, the IL-TIF gene is duplicated in other strains such as C57Bl/6, FVB and 129. The two copies, which show 98% nucleotide identity in the coding region, were named IL-TIF alpha and IL-TIF beta. Beside single nucleotide variations, they differ by a 658 nucleotide deletion in IL-TIF beta, including the first non-coding exon and 603 nucleotides from the promoter. A DNA fragment corresponding to this deletion was sufficient to confer IL-9-regulated expression of a luciferase reporter plasmid, suggesting that the IL-TIF beta gene is either differentially regulated, or not expressed at all.

Animals↗

PubMed2000

Phase I/II study of 2-chloro-2'-deoxyadenosine with cyclophosphamide in patients with pretreated B cell chronic lymphocytic leukemia and indolent non-Hodgkin's lymphoma.

Because of their substantial in vitro synergy, we conducted a dose-escalation study of cyclophosphamide (CP) added to 2-chloro-2'-deoxyadenosine (CdA) in patients with previously treated chronic lymphocytic leukemia and non-Hodgkin's lymphoma. CdA was given at a fixed dose (5.6 mg/m2/day) as a 2-h intravenous (i.v.) infusion, immediately followed by a 1-h i.v. infusion of CP, for 3 days. The initial daily CP dose was 200 mg/m2, and was escalated by 100 mg/m2 increments in successive cohorts of three to six patients to determine the maximum-tolerated dose (MTD). Additional patients were included at the MTD to extend toxicity and response analysis. Twenty-six patients received 68 cycles of chemotherapy. The MTD of CP after CdA 5.6 mg/m2, was 300 mg/m2. Acute neutropenia was the dose-limiting toxicity of this regimen, which was otherwise well tolerated. Delivery of repeated cycles was not feasible in eight patients (31%) because of prolonged thrombocytopenia. Severe infections were seen in three of 68 cycles (4%). The overall response rate was 58% (15 of 26; 95% CI, 36-76%), with 15% complete responses and 42% partial responses. These data show the feasibility of the association of CdA with CP. Given the response rate observed, further studies of this regimen are warranted in untreated patients, in particular with chronic lymphocytic leukemia and with Waldenström macroglobulinemia.

Adult↗

PubMed2000

Clonal monosomy 7 and 5q--in a child with myelodysplastic syndrome.

The authors report the case of a 5-year-old boy referred for thrombocytopenia and neutropenia. Bone marrow examination showed a myelodysplasia with clonal monosomy 7. The acceleration of the disease was marked by the appearance of an additional cytogenetic abnormality, i.e., the deletion of the long arm of chromosome 5 in the clonal cells. RAS gene mutation was not detected. Chemotherapy was started to achieve complete remission before a bone marrow transplantation. This treatment was complicated by a prolonged aplasia and the patient died of systemic mycotic infection.

Child, Preschool↗

PubMed1999

A new antigen recognized by cytolytic T lymphocytes on a human kidney tumor results from reverse strand transcription.

By stimulating blood lymphocytes from a renal cell carcinoma patient in vitro with the autologous tumor cells, we obtained cytolytic T lymphocyte (CTL) clones that killed several autologous and allogeneic histocompatibility leukocyte antigen (HLA)-B7 renal carcinoma cell lines. We identified the target antigen of these CTLs by screening COS cells transfected with the HLA-B7 cDNA and with a cDNA library prepared with RNA from the tumor cells. The antigenic peptide recognized by the CTLs has the sequence LPRWPPPQL and is encoded by a new gene, which we named RU2. This gene is transcribed in both directions. The antigenic peptide is not encoded by the sense transcript, RU2S, which is expressed ubiquitously. It is encoded by an antisense transcript, RU2AS, which starts from a cryptic promoter located on the reverse strand of the first intron and ends up on the reverse strand of the RU2S promoter, which contains a polyadenylation signal. This mechanism of antigen expression is unprecedented and further illustrates the notion that many peptides recognized by T cells cannot be predicted from the primary structure of the major product of the encoding gene. Antisense transcript RU2AS is expressed in a high proportion of tumors of various histological types. It is absent in most normal tissues, but is expressed in testis and kidney, and, at lower levels, in urinary bladder and liver. Short-term cultures of normal epithelial cells from the renal proximal tubule expressed significant levels of RU2AS message and were recognized by the CTLs. Therefore, this antigen is not tumor specific, but corresponds to a self-antigen with restricted tissue distribution.

Amino Acid Sequence↗

PubMed1999

Novel Philadelphia variant t(Y;9;22)(q12;q34;q11) in a case of chronic myeloid leukemia.

A novel Philadelphia (Ph) variant translocation, t(Y;9;22)(q12;q34;q11), was detected in a 63-year-old man with a newly diagnosed chronic myeloid leukemia (CML). Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed a b3a2 fusion transcript. Fluorescence in situ hybridization (FISH) utilizing library probes, subtelomeric cosmid probes, and probes hybridizing to the ABL and BCR genes showed a reciprocal three-way translocation involving Yq12, 9q34, and 22q11, and a BCR-ABL fusion signal on der(22). The subtelomeric Yq probe hybridizing centromerically to the IL9 receptor gene and covering the centromeric portion of the SYBL1 gene was found to be translocated to der(9).

Adult↗

PubMed1999

Digital clubbing in a patient with progressive mantle cell lymphoma.

Digital clubbing with or without hypertrophic osteoarthropathy may occur in a variety of neoplastic diseases. We present the first description of digital clubbing in a patient with progressive mantle cell lymphoma, in the absence of any other apparent etiology. We suggest that clubbing might be a paraneoplastic manifestation in mantle cell lymphoma. The literature on digital clubbing in hematological neoplasms is reviewed.

Diagnosis, Differential↗

PubMed1999

Unusual clinical course and acquisition of del(11)(q23) in second lymphatic blastic phase of a Ph-positive chronic myeloid leukemia.

We describe unusual clinical and cytogenetic findings of a 29-year-old female with a Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML), who showed a mosaic of apparently normal cells and cells bearing the classical t(9;22)(q34;q11) during the first lymphatic blastic phase (BP). The second lymphatic BP developed 10 years later. In addition to the t(9;22), which was detected in all metaphases, a del(11)(q23) was identified as a subclonal change in 4 of 25 metaphases. Fluorescence in situ hybridization (FISH) analysis using a chromosome 11-specific library probe and a probe covering the breakpoint cluster region of the MLL gene revealed hybridization signals of both probes on the normal and the deleted chromosome 11, indicating that the breakpoint on chromosome 11 occurred telomerically to the breakpoint cluster region of the MLL gene. Chemotherapeutic treatment resulted in reconstitution of the chronic phase with persistence of the Ph translocation as the sole chromosomal abnormality.

Adult↗

PubMed1999

Benign monoclonal gammopathy turning to AL amyloidosis after kidney transplantation.

The fate of preexisting benign monoclonal gammopathy after organ transplantation is largely unknown. We report the case of a 47-year-old male kidney graft recipient with a pretransplantation IgG kappa monoclonal gammopathy who developed, 10 years after transplantation, de novo augloid light chain (AL) amyloidosis involving skin and kidney graft. The potential role of heavy immunosuppressive treatment in the development of this complication is discussed. The possible occurrence of AL amyloidosis should be kept in mind when a patient with benign monoclonal gammopathy is evaluated for organ transplantation, as well as when a transplanted patient with pre-existing monoclonal gammopathy develops new onset of proteinuria.

Amyloidosis↗

PubMed1999

Application of the International Prognostic Scoring System for myelodysplastic syndromes.

BACKGROUND: In March 1997 an international workshop introduced a new International Prognostic Scoring System (IPSS) for MDS. The goal of the present study was to apply the IPSS to a large group of MDS patients from one centre and to compare it to the FAB-classification. PATIENTS: One hundred eighty-four MDS patients were included on the basis of similar criteria as used by the workshop but some of them (30) received AML-type therapy. RESULTS: The IPSS separated our patients into distinctive prognostic subgroups (P = 0.0001). Median survival was respectively 6.5, 2.6, 1.3 and 0.75 years for the low-risk (22% of patients), the intermediate-1-risk (INT-1) (46%), the intermediate-2-risk (INT-2) (25%) and the high-risk group (7%). The IPSS also discriminated within each of the FAB-categories: RA patients (58 patients) were present in low-risk, INT-1-risk and INT-2-risk subgroups, RARS patients (23) were separated into low-risk and INT-1-risk subgroups. RAEB patients (53) were distributed predominantly between INT-1-risk and INT-2-risk groups, RAEB-t patients (23) between INT-2-risk and high-risk subgroups. CMML patients (27) were present in the low-risk, the INT-1-risk and the INT-2-risk group. CONCLUSIONS: Our results confirm the effectiveness of the IPSS in predicting clinical outcome in MDS patients and indicate that it is an improved method compared to the FAB-classification.

Age Factors↗