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G Verhoef

Publications and source records attributed to G Verhoef.

At least 55 records · Page 3Linked to original sources
PubMed1997

BCL6 gene rearrangements also occur in marginal zone B-cell lymphoma.

Marginal zone B-cell lymphoma (MZBCL) represents a distinct subtype of B-cell non-Hodgkin's lymphoma (NHL) which has been recently recognized and defined as a disease entity. Cytogenetically, these lymphomas reveal a high prevalence of trisomy 3, and recent data obtained by comparative genomic hybridization indicate that the chromosomal regions 3q21-23 and 3q25-29 might be of particular pathogenetic significance. We identified structural chromosomal abnormalities involving the region 3q27 and rearrangements of the BCL6 proto-oncogene in three out of 34 (9%) well-defined cases of extranodal, nodal and splenic MZBCL using cytogenetic analysis. Southern blot, and fluorescence in situ hybridization (FISH). All three cases were characterized by a t(3;14)(q27;q32). Two of them showed additional chromosomal abnormalities including trisomy 3, which was found in one case. The patients displayed extranodal disease and did not demonstrate any striking clinical and histological differences when compared with MZBCL lacking BCL6 rearrangement. The present study for the first time demonstrates the occurrence of t(3;14)/BCL6 gene rearrangement in MZBCL, thus suggesting a role of the BCL6 proto-oncogene in the pathogenesis of MZBCL.

Aged↗
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

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

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

Prognostic significance of bone marrow trephine and peripheral blood smears in 55 patients with mantle cell lymphoma.

Bone marrow trephine and peripheral blood smears taken at diagnosis of 55 cases of well-documented mantle cell lymphomas were reviewed in order to analyse the leukaemic involvement in this non-Hodgkin's lymphoma: its incidence, morphological characteristics and prognostic significance. A median survival of 36 months was found. The median age was 61 and the male to female ratio was 4:1. Morphologically 7 cases presented with a mantle zone pattern, all the others had a diffuse pattern. Involvement of the bone marrow was found in 58% and a trend for prolonged survival in patients with a negative trephine was seen. An absolute lymphocytosis above 10,000 mu l was found at diagnosis in 5 cases (10%) and had a statistically significant impact on survival. An additional 5 cases developed frank leukaemia during the course of the disease and died within 1 to 6 months of this evolution, suggesting that marked lymphocytosis is more a terminal event associated with an extremely poor prognosis than a presenting symptom. Finally we identified an additional parameter with statistically prognostic significance, namely, the presence of atypical cells in the peripheral blood even in the absence of an increased lymphocytosis.

Adult↗
PubMed1996

Small B cell NHL and their leukemic counterpart: differences in subtyping and assessment of leukemic spread.

Three subtypes of small lymphocytic lymphoma were studied, namely B cell chronic lymphocytic leukemia (B-CLL), mantle cell lymphoma (MCL) and follicle center lymphoma (FCL). Agreement between tissue diagnosis, based on the proposal for a revised European-American classification of lymphoid neoplasms from the International Lymphoma Study Group, and the cytomorphological diagnosis on peripheral blood and/or bone marrow smears, using the proposals for the classification of chronic (mature) B and T lymphoid leukemias of the French-American-British Cooperative Group, was studied. Full agreement was found in 90% of the CLL and 82% of the FCL cases. In MCL cases, agreement was 65% including all cases classified as intermediate/mantle zone lymphoma according to FAB criteria. The incidence of bone marrow involvement detection in trephines compared to smears was equal in CLL (both 100%) and slightly higher in MCL (56 vs 48.5%); in FCL, however, trephine biopsies provided more reliable material (71 vs 35%).

Biopsy↗
PubMed1995

Polyclonal primitive hematopoietic progenitors can be detected in mobilized peripheral blood from patients with high-risk myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) form a heterogeneous group of clonal hematopoietic disorders with unfavourable prognosis. Allogeneic bone marrow transplantation is the only potentially curative treatment, but remains limited to a small subgroup of younger patients with HLA-compatible donors. As autologous stem cell transplantation is currently being explored as an alternative treatment strategy for MDS, more information needs to be acquired regarding the clonal nature of the progenitor cells in these autografts. Therefore, we have analyzed the clonal patterns of highly purified hematopoietic progenitors and their mature daughter cells in mobilized peripheral blood collections produced from five female patients with high-risk MDS in complete hematologic remission. X-chromosome activation patterns of flow-sorted immature (CD34 + 38low, CD34 + 33low) and committed (CD34 + 38high, CD34 + 33high) progenitors were studied with the polymerase chain reaction-based HUMARA assay. In four patients, a polyclonal remission was shown in all stem cell subpopulations and their mature daughter cells whereas one patient was found to remain skewed in all fractions, except T lymphocytes. This study provides strong evidence that polyclonal immature hematopoietic progenitors can be mobilized and harvested in patients high-risk MDS after treatment with high-dose chemotherapy.

Adult↗
PubMed1995

Comparative study of peripheral blood progenitor cell collection in patients with multiple myeloma after single-dose cyclophosphamide combined with rhGM-CSF or rhG-CSF.

Patients suffering from high-risk multiple myeloma (MM) were randomized to receive single high-dose cyclophosphamide followed by either rhGM-CSF or rhG-CSF in order to harvest circulating peripheral blood progenitor cells. The safety of the procedure, the mobilization kinetics, the relative efficacy of rhGM-CSF and rhG-CSF to mobilize progenitor cells and their relative toxicity were studied. Special attention was paid to the antigenic profile of CD34+ progenitor cells. Group I patients (n = 11) were treated with cyclophosphamide 4 g/m2 i.v. followed by rhGM-CSF at 10 micrograms/kg/d by subcutaneous administration. Group II (n = 11) patients received rhG-CSF s.c. at 10 micrograms/kg/d after the same dose cyclophosphamide. Both mobilization regimens appeared to be equally effective. No significant differences in absolute numbers of circulating progenitors, determined by CD34 expression or in yields of MNC, CFU-GM, BFU-E and CD34 subsets were observed. rhGM-CSF administration resulted however in delayed haemopoietic recovery and an increased complication rate. We conclude that rhG-CSF may be preferred because of its markedly lower toxicity and lower in-hospital costs.

Adult↗
PubMed1995

Mantle cell lymphoma: a clinicopathological study of 55 cases.

A recently described unifying proposal for mantle cell lymphoma has led to the formulation of strict diagnostic criteria based on morphology, immunology and molecular data to define this specific entity. Previous studies were often based on broader definitions such as centrocytic lymphoma, intermediately differentiated lymphoma or mantle zone lymphoma and, therefore, included a variety of entities with some, but not all, features ascribed to the mantle cell lymphoma. Since the publication of the unifying proposal no comprehensive studies have been published to confirm and support it. We selected 55 cases of mantle cell lymphoma collected in our institution in order to evaluate the validity of the proposal and, by using strict criteria, we analysed the morphological features, their variations and the changes occurring in the course of the disease as well as its clinical behaviour. The analysis of this material demonstrates that mantle cell lymphoma affects predominantly elderly males presenting with an advanced stage of disease. Twenty-four out of 55 patients died with, or of, the disease with a median survival of 32 months, even though most of them received aggressive chemotherapy. In all cases the histological features were strikingly uniform and most cases had a diffuse growth pattern. The neoplastic cells corresponded to small cleaved cells with a minimal variation in shape and size from one case to the other. The phenotype of the neoplastic cells was remarkably constant with expression of several pan-B cell markers, IgM, IgD and CD5, and lack of CD10 and CD23.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

A new t(2;5) translocation in a null cell type CD30 positive anaplastic large cell lymphoma case.

Anaplastic large cell lymphoma (ALCL) expressing the CD30 antigen is an uncommon subtype of non-Hodgkin's lymphoma characterized by distinct morphological and clinical features. The recurrent chromosomal abnormality found in these tumours is a t(2;5)(p23;q35) which has been detected in a minority of these cases, predominantly with a T cell immunophenotype. We report here a CD30 positive null cell type ALCL case cytogenetically characterized by a new type of t(2;5) translocation with distinct breakpoints at 2q37 and 5q31. FISH with a panel of 5q specific DNA probes applied in this case allowed for a mapping of a 5q31 breakpoint region between the locus for IL-3 (proximally) and CI5-56 probe (distally). These results point to a localization of unknown gene(s) on the long arm of chromosome 5 that, in addition to the NPM gene at 5q35, may be involved in the pathogenesis of some CD30+ ALCL.

Adult↗
PubMed1995

Translocation (11;15)(q23;q14) in three patients with acute non-lymphoblastic leukemia (ANLL): clinical, cytogenetic and molecular studies.

We report on three patients with acute non-lymphoblastic leukemia (ANLL) displaying the same chromosomal translocation t(11;15)(q23;q14). The clinical course of the disease was aggressive, and survival was short. The FAB subtype was M-2 in two cases, and M-1 in the remaining patient. Immunologically two cases showed aberrant expression of a lymphoid antigen (CD19 and TdT, respectively). HTRX1/MLL gene was rearranged in one patient studied at the time of diagnosis. These results plus data scattered in the literature show that the t(11;15)(q23;q14) can be added to the list of recurrent rearrangements in ANLL involving 11q23.

Adult↗
PubMed1995

Cytogenetic analysis of B cell chronic lymphoid leukemias classified according to morphologic and immunophenotypic (FAB) criteria.

609 patients with B cell chronic lymphoproliferative disorder were studied with the primary aim of analyzing the cytogenetic profile of B cell chronic lymphocytic leukemias and, if possible, define correlations with FAB classification of these diseases. Morphological and immunological studies were performed according to criteria proposed by the FAB group. A panel of monoclonal antibodies, including at least sIg, CD19, CD5, and FMC7 was used. Interpretations of morphology and cytogenetics were made independently. When applying strict FAB criteria 65% of the cases could be classified. Most of them (44%) were chronic lymphocytic leukemia (CLL). The cases not satisfying strict FAB criteria could be divided into two groups: one closely related to CLL, and here defined as atypical CLL (aCLL) (21%) and another group consisting of patients with leukemic manifestations of B cell non-Hodgkin's lymphoma (LL) (14%). Analyzable metaphases were obtained in 89% of patients. Clonal abnormalities were present in 35% of patients. The most frequent chromosomal changes were abnormalities of chromosome 11q (60 cases), trisomy 12 (46 cases) and structural rearrangements of chromosome 14q (44 cases). Statistical associations with FAB subtypes were found: aCLL and trisomy 12 (P < 0.00001); mantle zone lymphoma (MZL) and t(11;14) (P < 0.00001) and del(6)(q) (P < 0.0001); CLL/mixed cell type and del(6)(q) (P < 0.002); follicular lymphoma and t(14;18) (P < 0.00001); splenic lymphoma with villous lymphocytes and del(7)(q) (P < 0.0004); leukemic lymphoma (LL) with rearrangements in chromosome 9q (P < 0.0001) and trisomy of 3 (P < 0.001). Chronic lymphocytic leukemia was not statistically associated with any specific chromosomal abnormality. However, this subtype showed a high incidence of del(11)(q) and rearrangements of 13q. This study confirms the value of cytogenetic investigation in the diagnosis of these disorders and may provide some new elements for future refinement of the FAB classification in mature B cell lymphocytic disorders.

Chromosome Aberrations↗
PubMed1994

t(1;19) without detectable E2A rearrangements in two t(14;18)-positive lymphoma/leukemia cases.

Translocation t(1;19)(q23;p13) plays a crucial role in the pathogenesis of childhood pre-B cell leukemia and results in the formation of a fusion gene E2A-PBX1 that encodes a hybrid transcription factor with oncogenic potential. Here we describe two cases, one follicular lymphoma and one acute lymphoblastic leukemia/lymphoma, characterized by a complex karyotype including t(14;18), t(8;14), as well as t(1;19). Molecular studies in both cases failed to show rearrangements of the E2A gene. These results suggest that the t(1;19) found as a secondary chromosome change in t(14;18)-positive lymphoma/leukemia might be a molecular variant of the t(1;19) that is typical of childhood pre-B cell leukemia.

Blotting, Southern↗
PubMed1994

"Jumping" translocation of 9q in a case of follicular lymphoma.

Cytogenetic and fluorescence in situ hybridization (FISH) studies on a t(14;18)-positive follicular lymphoma presenting a remarkable pattern of secondary chromosomal changes are reported. Chromosome analysis of a lymph node biopsy performed at diagnosis revealed the presence of four related subclones characterized by the (14;18) translocation alone or together with one of the following anomalies: add(1)(p36), add(13)(q34), or der(12)(12;13)(q24;q14)add(13)(q34). The chromosome 9 origin of the extra material on the abnormal chromosomes 1 and 13 was demonstrated by FISH and points to "jumping" translocation in the present case.

Chromosomes, Human, Pair 9↗