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Biomedical subjects

C Mecucci

Publications and source records attributed to C Mecucci.

At least 73 records · Page 4Linked to original sources
PubMed1997

Identification of chromosome changes in acute myeloid leukemia (AML-M2) by molecular cytogenetics.

Karyotyping with fluorescence in situ hybridization (FISH) is reported in two rare cases of AML-M2 FAB. In the first case FISH analysis confirmed the presence of a t(7;11)(p15:p15) translocation in a complex karyotype that also showed an unbalanced translocation involving the other chromosome 7, a rare rearrangement between chromosomes 9 and 20, and four or five copies of a small marker derived from chromosome 9. In the second case whole chromosome painting with probes for chromosomes 8, 14, and 21 revealed the presence of a masked t(8;21) translocation in which one chromosome 14 was involved in a newly discovered rearrangement, i.e., t(8;14;21)(q22-q24;q11;q22). Moreover , double color FISH using ETO-CDR P1 probe and a cosmid for the 5' part of AML-1 on chromosome 21 showed a two color signal on the 8q-, suggesting a recombination between ETO and AML 1. Molecular cytogenetics overcomes limitation of chromosome banding in the interpretation of complex rearrangements.

Adult↗
PubMed1997

Further characterization of morphologically defined typical and atypical CLL: a clinical, immunophenotypic, cytogenetic and prognostic study on 390 cases.

We analysed a group of 390 patients, diagnosed with chronic lymphocytic leukaemia (CLL). Cases were subclassified as morphologically typical and atypical CLL according to the criteria of the FAB proposal. Typical CLL cases were mostly diagnosed at a low-risk stage (Binet A/Rai 0), required no immediate treatment and expected a long survival; atypical CLL cases mostly presented at a more advanced risk stage (Binet B/Rai I-II), usually required immediate treatment and their survival was shorter. Moreover, clinical staging was of prognostic significance in typical but not in atypical cases. In typical CLL, del(11q) was the most common chromosomal abnormality (21%) whereas in atypical CLL trisomy 12 was found in about 65% of the cases documented with an abnormal karyotype. Although chromosomal abnormalities were associated with a poor survival in typical CLL, they are of no prognostic significance in atypical CLL. Based on these data, we conclude that subtyping CLL by morphology enables the identification of two groups of cases, each characterized by a specific clinical presentation, different cytogenetic abnormalities and prognostic parameters. We speculate that these two groups may represent two related, but different, diseases with different prognostic parameters and a different survival.

Chromosome Aberrations↗
PubMed1997

FISH identifies different types of duplications with 12q13-15 as the commonly involved segment in B-cell lymphoproliferative malignancies characterized by partial trisomy 12.

Clinical, cytogenetic, fluorescence in situ hybridization (FISH), and Southern blot data of 18 patients with different subtypes of B-cell non-Hodgkin's lymphoma, cytogenetically characterized by partial trisomy 12, are presented. These chromosomal changes occurred predominantly in clinically progressive chronic lymphocytic leukemia, mixed cell type, and advanced-stage follicle center cell lymphoma at the time of relapse or transformation into diffuse large cell lymphoma. Partial trisomy 12 consistently included the long arm of chromosome 12, either completely or partially, and resulted from dup(12q) or other rearrangements involving chromosome 12. The duplications were cytogenetically identified as dup(12)(q13q23), dup(12)(q13q22), or dup(12)(q13q15) in follicle center cell lymphoma or t(14;18)-positive diffuse large cell lymphoma; dup(12)(q13q22) or dup(12)(q13q24) in chronic lymphocytic leukemia; and dup(12)(q13q21) in a case of t(14;18)-negative diffuse large cell lymphoma. FISH, using library probes and a panel of YAC probes, mapped along the long arm of chromosome 12, confirmed the cytogenetic results in all cases analyzed except for three cases of t(14;18)-positive follicle center lymphoma or diffuse large cell lymphoma with dup(12q). In these cases, FISH showed similar, possibly identical, duplications, which involved a region more centromeric (12q11-21) than assumed by karyotypic analysis (12q13-22 or 12q13-23) and included alphoid DNA sequences, a combination hitherto unknown. In addition, commonly duplicated regions of chromosome 12 could be defined: 12q11-21, including alphoid DNA sequences for follicle center cell lymphoma or t(14;18)-positive diffuse large cell lymphoma, 12q13-22 for chronic lymphocytic leukemia, and 12p13-q15 for marginal zone cell lymphoma, all of which overlapped in 12q13-15. Whether these regions, especially 12q13-15, may contain genes which are important in malignant transformation or disease progression of B-cell lymphoproliferative malignancies characterized by complete or partial trisomy 12 remains to be determined.

Aged↗
PubMed1996

ider(9)(q10)t(9;22)(q34;q11) is a recurrent chromosomal abnormality in acute lymphoblastic leukemia and lymphatic blastic phase of chronic myelogenous leukemia.

We report on two cases, one with acute lymphoblastic leukemia and a second with lymphatic blastic phase of Philadelphia chromosome-positive chronic myelogenous leukemia, cytogenetically characterized by ider(9)(q10)t(9;22)(q34;q11). Our findings and the data of the 4 cases previously published indicate that ider(9)(q10)t(9;22)(q34;q11) represents a rare but recurrent chromosomal abnormality occurring in hematological malignancies with lymphoid differentiation, namely acute lymphoblastic leukemia and lymphatic blastic phase of chronic myelogenous leukemia, and most likely evolves from a preexistent der(9) involved in the standard t(9;22).

Adult↗
PubMed1996

Biallelic alterations of both ETV6 and CDKN1B genes in a t(12;21) childhood acute lymphoblastic leukemia case.

Recently, a new recurrent t(12;21)(pl3;q22) has been identified in a B-cell lineage childhood acute lymphoblastic leukemia (ALL). The translocation results in a fusion of two known genes, ETV6/TEL (12p13) and AML1 (21q22), previously shown to be involved in the pathogenesis of myeloid disorders. We report results of cytogenetic fluorescence in situ hybridization and molecular studies of a B-cell childhood common ALL with a cryptic 12;21 translocation. Aberrations identified in this case involve both chromosomes 12 and include not only the ETV6-AML1 gene fusion and two different microdeletions of ETV6 but also the hemizygous loss of CDKN1B, D12S119, and KRAS2 loci and a putative rearrangement of the second CDKN1B allele as a result of an inv(12)(p13q24). Moreover, it was shown that the AML1-ETV6 reciprocal chimeric transcript was not present in the malignant cells, and hence may not play a major role in leukemogenesis. In addition, the putative loss of wild-type function of CDKN1B and ETV6 could indicate a synergistic effect of both genes in the pathogenesis of this leukemia case.

Adolescent↗
PubMed1996

Marginal zone B-cell lymphomas of different sites share similar cytogenetic and morphologic features.

Clinical, histologic, cytogenetic, and molecular genetic data of 31 patients with extranodal, nodal, and splenic marginal zone B-cell lymphoma (MZBCL) are presented. Despite these variable clinical manifestations, a similar spectrum of morphologic features as well as distinctive immunophenotypic findings were noted. In all cases, a monotypic B-cell proliferation consistently negative for CD5, CD10, and CD23 was found expanding the marginal zone of the B follicle with and without colonization of the follicle centers. Clonal chromosomal abnormalities were detected in 23 of the 31 patients. Recurrent aberrations included whole or partial trisomy 3 (18 cases), trisomy 18 (9 cases), and structural rearrangements of chromosome 1 with breakpoints in 1q21 (9 cases) or 1p34 (6 cases), all of which were seen in extranodal, nodal, as well as splenic MZBCL. Abnormalities of the additional chromosome 3, such as +del(3)(p13),+i(3)(q10), or structural changes involving the distal part of the long arm, were evident in 9 of the 18 cases. All recurrent abnormalities were found in MZBCL more frequently than in other histologic entities of B-cell non-Hodgkin's lymphoma (B-NHL). None of the known lymphoma-associated chromosomal changes or rearrangements of the BCL1, BCL2, BCL3, BCL6, and CMYC genes were detected. We conclude that MZBCL represent a distinct entity of B-NHL with characteristic morphologic and immunophenotypic features and particular chromosomal abnormalities, and that a close histogenetic relationship between extranodal, nodal, and splenic MZBCL is likely, although the clinical presentation may vary.

Adult↗
PubMed1996

14q+ chromosome marker in a T-cell-rich B-cell lymphoma.

Cytogenetic, in situ hybridization, and molecular studies were performed in a case of T-cell-rich B-cell lymphoma. Demonstration of Ig gene rearrangements for both heavy and light chains confirmed the B-lineage restriction of the neoplastic cell population. Moreover, as expected in B-cell malignancies, all abnormal karyotypes showed a 14q+ chromosome marker involving 14q32. The origin of the extra material on the derivative 14q+, as defined by chromosome painting with a library for chromosome 11, and Southern blotting for c-myc and bcl-2 rearrangements, remains unknown.

Blotting, Southern↗
PubMed1996

BCL-6 expression in reactive lymphoid tissue and in B-cell non-Hodgkin's lymphomas.

Chromosomal abnormalities involving 3q27 have recently been associated with diffuse large B-cell lymphomas and, less frequently, with follicular lymphomas. Molecular studies have led to the identification of the BCL-6/LAZ-3 gene, located at 3q27 and coding for a putative zinc-finger protein that might act as a transcriptional regulator during cell differentiation and development. Rearrangement of BCL-6 results in truncation of the gene in its 5' portion, leaving the protein intact; a resultant deregulation of its expression has been hypothesized. In order to test this hypothesis, the expression of BCL-6 protein was investigated in human reactive lymphoid tissue and compared with a group of non-Hodgkin's lymphomas (NHLs) with or without 3q27 anomalies and/or BCL-6 gene rearrangement. BCL-6 protein is consistently expressed in reactive lymphoid tissues, where it is restricted to the follicle centre. The protein is also widely expressed in NHL: all follicular lymphomas tested showed a pattern of expression similar to the reactive B follicle, independently of the presence of BCL-6 gene rearrangement and/or 3q27 anomalies. In the diffuse large B-cell lymphomas, there was more variation in BCL-6 expression, but a correlation with 3q27 anomalies and/or BCL-6 rearrangement was not found. Deregulation of the BCL-6 gene did not result in an aberrant tissue expression as detected by immunohistochemistry.

Antibody Specificity↗
PubMed1996

BCL3 rearrangement and t(14;19)(q32;q13) in lymphoproliferative disorders.

Translocation t(14;19)(q32;q13) is a rare but recurrent abnormality in chronic lymphocytic leukemia and small cell lymphoma. It has been associated with rearrangements of the BCL3 gene, which is located at the breakpoint on chromosome 19 and is juxtaposed to the immunoglobulin heavy chain locus on chromosome 14 as a result of the translocation. This results in transcriptional up-regulation of the BCL3 gene, which encodes a transcription coactivator, an I-kappa B protein, probably contributing to disease progression. We found, among 4,487 cytogenetic analyses of lymphoproliferative disorders, six cases with a t(14;19)(q32;q13), five of which showed the classical t(14;19)(q32;q13) and one of which showed a three-way translocation t(7;19;14)(q21;q13;q32). The 14;19 translocation never occurred as a single abnormality; additional aberrations included trisomy 12 and several structural abnormalities. The cytogenetic examination was supplemented by molecular analysis using available probes for the BCL3 locus (p alpha 1.4P and p alpha 5B) in 1,150 of the 4,487 patients. Rearrangements of BCL3 could be detected in five cases, all of which had the classical t(14;19). In the case with t(7;19;14), the suspected BCL3 involvement could only be confirmed using long-range restriction mapping, indicating that, with the usually available BCL3 probes, rearrangements of this locus may be missed.

B-Cell Lymphoma 3 Protein↗
PubMed1996

Successful use of the same slide for consecutive fluorescence in situ hybridization experiments.

The feasibility of using the same slide repeatedly for fluorescence in situ hybridization (FISH) experiments was systematically evaluated by applying standard procedures and various combinations of direct- and indirect-labeled probes to slides from patients with hematologic malignancies. Specific and distinct hybridization signals along with weak background signals and chromosome morphology of good to moderate quality could be obtained in up to three experiments performed consecutively on the same slide. Signals related to biotin- or digoxigenin-labeled probes applied in previous hybridizations were still visible with variable intensity, but interpretation problems that may result from this signal noise can be avoided by using adequate probes, detection systems and fluorochromes, and sequence of experiments.

Biotin↗
PubMed1996

Translocation (Y;1)(q12;q12) in hematologic malignancies. Report on two new cases, FISH characterization, and review of the literature.

Translocation (Y;1)(q12;q12) is a rare cytogenetic anomaly occurring in hematologic disorders thought to affect stem cells. We report here on two new cases, one end-stage myelofibrosis and one chronic myelomonocytic leukemia. The translocation breakpoints were assessed by conventional cytogenetic techniques in both cases and by FISH in the second case. A partial trisomy of the 1q21-qter region could be demonstrated. The data of the literature are reviewed and the possible pathogenetic mechanisms are discussed.

Adolescent↗
PubMed1996

Dicentric (1;15) in myeloid disorders.

We report three cases of myeloid disorders with a dic(1;15)(p11;p11), resulting in trisomy of the long arm of chromosome 1. A review of the literature showed six cases, reported as t(1;15). We suggest that these cases have the same anomaly and should be reappraised as dic(1;15).

Adult↗
PubMed1996

Trisomy 3 in marginal zone B-cell lymphoma: a study based on cytogenetic analysis and fluorescence in situ hybridization.

Trisomy 3 represents the most frequent and consistent chromosomal abnormality characterizing the recently defined entity marginal zone B-cell lymphoma (MZBCL). By cytogenetic analysis and/or fluorescence in situ hybridization (FISH) on interphase nuclei we found in increased copy number of chromosome 3 in 22/36 (61%) successfully analysed cases, including 8/12 cases with extranodal MZBCL, 8/13 cases with nodal MZBCL, and 6/11 patients with splenic MZBCL. Sensitivity of interphase cytogenetics was somewhat higher than that of conventional cytogenetic investigation. Structural chromosomal changes involving at least one chromosome 3 were seen in 11/20 cases with an increased copy number of chromosome 3: +de(3)(p13) was demonstrated in three cases, and was the sole chromosomal abnormality in one of them; +i(3)(q10) was seen in two other patients; and rearrangements involving various breakpoints on the long arm of chromosome 3 were found in the remaining cases. FISH on metaphase spreads confirmed these structural abnormalities and additionally showed two unexpected translocations involving chromosome 3. We conclude that: (1) trisomy 3 occurs in a high proportion of extranodal, nodal and splenic MZBCL; (2) FISH on interphase nuclei is an additional and sensitive tool in detecting an increased copy number of chromosome 3 in MZBCL; (3) additional structural abnormalities involving the long arm of chromosome 3 are frequent but non-recurrent and are perhaps secondary changes; and (4) abnormalities such as +del(3)(pl3) and +i(3)(q10) suggest that genes located on the long arm of chromosome 3 are of particular importance in the pathogenesis of MZBCL.

Adult↗
PubMed1996

Deletions of the long arm of chromosome 7 in myeloid disorders: loss of band 7q32 implies worst prognosis.

Clinical and cytogenetic data were analysed in 54 patients with acute non-lymphocytic leukaemias (ANLL) or MDS (myelodysplastic syndromes) and deletion of the long arm of chromosome 7 (7q-), in order to determine if there is a commonly deleted region in 7q and to establish possible correlations between karyotypic features, such as karyotype pattern, karyotype complexity, associated anomalies, and/or the type of deleted segments, and outcome of patients with these disorders. The median follow-up of our patients was 4 months (range 1-89), as was the median survival. In 30% of the cases there was a history of preceding MDS or previous chemotherapy. Clinical and cytogenetic remission was obtained in 7/36 patients treated with chemotherapy (CT). At the time of 7q- detection, three patients previously treated with CT for ANLL were in clinical remission. 5q- was the most recurrent associated abnormality. Complex karyotypes were observed in 68% of the cases. In univariate analysis, statistical differences in survival were observed according to diagnosis (therapy-related and secondary diseases had a worse prognosis than primary disorders), the chromosomal segments deleted (the loss of band 7q32 was of poor prognostic value), the karyotype complexity (patients with single anomalies did better than patients with complex anomalies) and the response to therapy (patients who achieved complete remission had a better survival probability). In multivariate analysis, the loss of band 7q32 was found to be significantly related to very poor prognosis. This finding suggests that band 7q32 may contain critical genes that should be explored at the molecular level.

Adolescent↗
PubMed1996

"Small" B-cell non-Hodgkin's lymphomas with splenomegaly at presentation are either mantle cell lymphoma or marginal zone cell lymphoma. A study based on histology, cytology, immunohistochemistry, and cytogenetic analysis.

Only 1 to 2% of all non-Hodgkin's lymphomas (NHL) present with an enlarged spleen, most of them "small B-cell lymphomas." Recently, several reports have identified these lymphomas as marginal zone B-cell lymphomas. We reviewed 39 cases of NHL presenting with an enlarged spleen without lymphadenopathy, documented by fixed and frozen material. Two were peripheral T-cell lymphomas, four diffuse large B-cell lymphomas, and 14 hairy cell leukemias. The remaining 19 belonged to the "small B-cell" category and constitute the focus of our study. Subtyping was achieved by combining morphology, immunophenotype, and cytogenetic features according to the proposal of the International Lymphoma Study Group; in addition, analysis of the peripheral blood and bone marrow smears was performed adopting the French-American-British (FAB) criteria. From this study, we can conclude that most "small B-cell" NHL of the spleen were either mantle cell lymphomas or marginal zone cell lymphomas and, by peripheral blood analysis, that the mantle cell lymphomas corresponded to intermediate lymphocytic lymphoma and the marginal zone cell lymphomas to splenic lymphomas with villous lymphocytes. As a result, several diagnostic criteria can be proposed that may be helpful in differentiating mantle cell lymphoma from marginal zone cell lymphoma in the spleen.

Adult↗
PubMed1996

The ETV6, CDKN1B and D12S178 loci are involved in a segment commonly deleted in various 12p aberration in different hematological malignancies.

Structural rearrangements including deletions of the short arm of chromosome 12 are frequent cytogenetic findings in various hematologic malignant disorders. Using FISH with a panel of DNA probes we detected loss of a common region of 12p in 22 patients with different hematologic disorders. Nine of them were characterized cytogenetically by a del(12p), seven by unbalanced translocations, and in the remaining cases the loss of the 12p region was masked by translocations and insertions, adding extra material to the short arm of chromosome 12. The smallest commonly deleted region found in all cases analyzed included ETV6, the gene for p27kipl (CDKN1B), and the D12S178 marker.

Adult↗
PubMed1996

ETV6 gene rearrangements in hematopoietic malignant disorders.

Chromosomal abnormalities involving the short arm of chromosome 12 have been frequently observed in a broad spectrum of hematological malignancies. Recently, a gene located in this chromosomal region and implicated in leukemogenesis was identified. The gene, called ETV6 (previously known as TEL) is a new member of the ETS family, a group of genes thought to act as transcriptional activators. The gene spans 240 kb and consists of eight exons coding for a helix-loop-helix (HLH) and a DNA-binding domain. ETV6 was originally identified in a t(5;12)(q33;p13) occurring in a chronic myelomonocytic leukemia (CMML). Recent reports, however, show its involvement in a growing number of translocations associated with myeloid as well as lymphoid leukemias. At the molecular level fusions of ETV6 with PDGFRB (5q33), ABL (9q34), MNI(22q11) and AML1(21q22) have already been identified. Analysis of these chimeric proteins indicates that distinct domains of ETV6 can be involved in different fusion products, thus ETV6 can provide transcriptional and dimerization properties for partner genes, or the gene itself can act as an altered transcriptional factor. At least two clinico-pathological entities associated with ETV6 rearrangements have emerged as distinct disorders. The first one is a chronic myeloid malignancy characterized by t(5;12)(q33;p13), monocytosis and/or eosinophilia. The second entity is a type of childhood acute lymphoblastic leukemia (ALL) hallmarked by t(12;21)(p13;q22), and is shown to be the most frequent but cytogenetically largely undetectable chromosomal anomaly in childhood ALL.

Chromosome Mapping↗