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G Castoldi

Publications and source records attributed to G Castoldi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Molecular cytogenetic characterization of marginal zone B-cell lymphoma: correlation with clinicopathologic findings in 14 cases.

BACKGROUND AND OBJECTIVES: To improve the definition of the incidence and significance of chromosome lesions occurring in marginal zone B-cell lymphoma (MZBCL). DESIGN AND METHODS: Fourteen cases of MZBCL diagnosed according to the REAL classification were studied by conventional chromosome analysis (CCA) and by interphase fluorescence in situ hybridization (FISH) using the following probes: 3q27/BCL6, 6q21, 7q31, 9p21/p16, 11q22/ATM, 13q14, 17p13, centromeres of #3, #7, #12. Pertinent clinical data were collected. RESULTS: Primary disease presentation consisted of histologically documented splenic MZBCL in 9 cases, nodal MZBCL in 3 cases and extra-nodal MZBCL in 2 cases. Four cases showed evolution into a high-grade lymphoma, due to the presence of a predominant large cell or blast cell component. Clonal karyotype anomalies were detected by CCA in 12 cases, 6 of which had a complex karyotype, including all 4 cases with high-grade histology. Interphase FISH confirmed cytogenetic data and revealed several cryptic chromosomal lesions. Overall, total/partial +12 was found in five cases; 13q14 and 17p13 deletion were found in four cases each; +3, 7q31 deletion and a BCL6 split signal were found in three cases; deletions at 6q21 and 11q22.3 in two cases each; +7 and a 9p21 deletion were found in one case each. INTERPRETATION AND CONCLUSIONS: i) Besides +3 and 7q-, 13q14 deletion, total/partial +12, BCL6 rearrangement, and deletions at 6q21, 11q22-23, and 17p13.3 are relatively frequent events in MZBCL; ii) unlike in mantle cell lymphoma, 9p21 deletion occurred infrequently in MZBCL; iii) a switch into high grade histology is usually associated with complex chromosome defects, including 6q-, 11q-, +12, and 17p.

Adult↗
PubMed2001

Multilineage involvement in the 5q- syndrome: a fluorescent in situ hybridization study on bone marrow smears.

BACKGROUND AND OBJECTIVES: A pluripotent progenitor cell was demonstrated to be involved in myelodysplastic syndromes (MDS) with normal karyotype or with numerical chromosome aberrations, but the pattern of lineage involvement by the 5q31 deletion in the 5q- syndrome is unknown. We performed this study in order to define the distribution pattern of the 5q- anomaly better in the non-lymphoid cell compartment DESIGN AND METHODS: Bone marrow (BM) smears from 8 patients with the 5q- syndrome were studied by a modification of the fluorescent in situ hybridization (FISH) technique that allowed direct visualization of cell morphology. A commercial LSI EGR1 probe (Vysis Inc.) for the 5q31 band was used simultaneously in dual-color experiments with a chromosome-5-centromeric probe (Vysis Inc.) on BM smears from 8 patients with the 5q-syndrome. As additional internal controls a chromosome-7-centromeric probe and a 7q31 probe were used. To establish the sensitivity limit of this approach 5 normal BM smears were studied. All 8 patients had the 5q- chromosome as the sole anomaly in 45% to 75% of the interphase cells. RESULTS: For each patient 20-40 erythroblasts were analyzed: they were mostly proerythroblasts and basophilic erythroblasts. In all patients a clone carrying the 5q31 deletion was detected (35-50% of the cells, median 45%). Between 20-50 granulocyte precursors were scored; the 5q31 deletion was found in 40%-50% (median 45%) in all cases. The proportion of neutrophils carrying the 5q deletion was consistently lower than the corresponding value in promyelocytes (28.7% vs 45.6%). In the 20-25 megakaryocytes analyzable in all patients, the overall incidence of 5q31 deletion was 52-68%. Equal proportions of large multilobular megakaryocytes and hypolobular megakaryocytes characteristic of the 5q- syndrome were scored: the latter cells showed the 5q31 deletion more frequently than the former cells (93.6% vs 19.3% of the cells). In 66% to 100% of the cases (median 83%) a few cells with uncondensed nuclear chromatin pattern, and two or three prominent nucleoli with cytoplasmatic hypogranulation were seen in each sample carrying the 5q31 deletion. INTERPRETATION AND CONCLUSIONS: We arrived at the following conclusions: i) the transformation in the 5q- syndrome involves an early progenitor cell retaining the ability to proceed along multiple differentiation pathways; ii) there is a preferential distribution of the 5q31 deletion within immature cells and morphologically abnormal megakaryocytes.

Adolescent↗
PubMed2001

Response to fludarabine in B-cell chronic lymphocytic leukemia patients previously treated with chlorambucil as up-front therapy and a CHOP-like regimen as second line therapy.

BACKGROUND AND OBJECTIVES: Fludarabine (FAMP) is the most active single agent in relapsed and refractory patients with B-cell chronic lymphocytic leukemia (B-CLL). However, it is not clear whether it should be used immediatly after failure of chlorambucil (CLB). We addressed such an issue retrospectively analyzing a series of patients in whom FAMP was used as third-line therapy after a sequential use of CLB and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CHOP-like regimen, respectively. DESIGN AND METHODS: On a retrospective basis, 57 B-CLL patients fulfilling the above mentioned criteria and followed-up in seven different hematologic institutions, were evaluated. RESULTS: Of 57 patients who were evaluated for response, 3 (5.2%) achieved a complete response (CR), 30 (52.6%) had a partial response (PR) and the remaining 24 (42.1%) failed to respond to FAMP. Overall median survival from the start of FAMP therapy was 30 months. Survival by tumor response did not show any difference between responders and non-responders (p = 0.536). The survival was significantly shorter in the group of patients with progressive disease than in all other patients included in our study (p = 0.05). Using each patient as his own control (McNemar test) we attempted to evaluate the value of FAMP in inducing a therapeutic response after failure of previous therapies. Among the 37 patients resistant to CLB the response rate was 40.3% with FAMP (p = 0.037) and only 17.5% with CHOP (p = 1.0). Among 35 patients resistant to a CHOP-like regimen, the response rate was 29.8% (p = 0.066) after FAMP therapy. INTERPRETATION AND CONCLUSIONS: From our results, it seems that FAMP works better than a CHOP-like regimen in patients resistant to CLB although results do not translate into a survival advantage for responders.

Adult↗
PubMed2000

Angiotensin II increases calponin expression in cultured rat vascular smooth muscle cells.

Angiotensin II (Ang II) action on vascular smooth muscle cells is not limited to contraction, but includes long term effects such as hypertrophy and hyperplasia. This implies a complex pattern of gene modulation, which remains largely unknown. We used the mRNA differential display method to screen rat aortic smooth muscle cells cultured with or without Ang II. We demonstrated that Ang II induces the expression of calponin, a 34-kD protein, which has been shown to regulate smooth muscle cell contraction and to be a marker of smooth muscle cell differentiation. We demonstrated this induction both at gene and protein level in vascular smooth muscle cells. Calponin mRNA was dose-dependently induced by Ang II, with an effect still evident at 5 x 10(-9)M, and it did not require active protein synthesis, since cycloheximide treatment did not suppress this induction. Calponin gene expression was maximal at 3 h, while protein expression was maximal at 8 h. Calponin expression was completely abolished by the AT1 receptor antagonist, losartan, at 1 x 10(-6)M. Our data demonstrate that Ang II increases calponin gene expression and protein level in rat aortic smooth muscle cells in vitro.

Analysis of Variance↗
PubMed2000

PCR with degenerate primers for highly conserved DNA polymerase gene of the herpesvirus family shows neither human herpesvirus 8 nor a related variant in bone marrow stromal cells from multiple myeloma patients.

The possibility has been raised that either a human herpesvirus-8 (HHV-8) variant or a novel, unidentified, gamma-herpesvirus related to HHV-8 is frequently associated with multiple myeloma (MM), which could explain the lack of antibodies to HHV-8 antigens and the discordant results from polymerase chain reaction (PCR) studies of HHV-8-specific sequences in MM patients. Thus, we used a sensitive PCR assay with degenerate primers targeting the highly conserved DNA polymerase gene of the herpesvirus family to examine the long-term cultures of bone marrow stromal cells (BMSCs) from 19 MM, 3 monoclonal gammopathies of undetermined significance and 6 control patients. Both the culture supernatant and the adherent stromal layer were examined from the 2nd until the 8th week of culture to assess the immunophenotype of the various cell types harvested for the molecular analysis. BMSCs consisted of a mixed population of fibroblast, macrophage, dendritic and endothelial cells. An amplified product of the expected size was obtained only in 3 MM cases, both in the adherent and nonadherent fractions. Direct sequencing and alignment of the nucleotide and amino acid sequences showed that the DNA sequences were 100% identical to Epstein-Barr virus (EBV) DNA. The PCR positivity was due to the presence of EBV-infected lymphoblastoid cells with plasmacytoid features, expressing the EBV-encoded latent membrane protein-1 and detectable either in the stromal cells or in the culture supernatant. Our data do not support a causal role of either HHV-8 or a novel herpesviral variant related to HHV-8 in MM.

Adult↗
PubMed2000

A 3-cM commonly deleted region in 6q21 in leukemias and lymphomas delineated by fluorescence in situ hybridization.

Deletions of the long arm of chromosome 6 (6q) are frequent chromosome aberrations in non-Hodgkin lymphomas (NHLs) and acute lymphoblastic leukemias (ALLs). It is presumed that one or more tumor suppressor genes are localized on 6q. By means of fluorescence in situ hybridization (FISH), we attempted to detect and delineate deletions of 6q in leukemias and lymphomas. We performed FISH on 148 cases of lymphoma and acute leukemia using a panel of 36 YAC probes distributed from 6q12 to 6q27 and a centromeric probe of chromosome 6 as internal control. Deletions of 6q that included a 7-cM commonly deleted region in 6q21 were detected in 59 patients who had B- and T-cell low-grade and high-grade NHL and ALL. FISH with two YAC probes flanking this region was performed on an additional 97 cases of NHL and leukemia. Deletions in 6q21 were detected in an additional 21 cases. In five cases of high-grade B- and T-cell NHL and ALL, the deletion breakpoints were located within the commonly deleted region. To define the deletion breakpoints exactly and to narrow this region further, FISH was performed with six additional YAC probes that have been physically localized within this region. A 3-cM (4-5 Mb) commonly deleted region in 6q21 was delineated. Our study suggests that this commonly deleted region harbors a putative tumor suppressor gene involved in the pathogenesis of both low-grade and high-grade NHL and ALL. Genes Chromosomes Cancer 27:52-58, 2000.

Chromosome Deletion↗
PubMed2000

Clinical, hematological and cytogenetic characteristics of atypical chronic myeloid leukemia.

BACKGROUND: Atypical chronic myeloid leukemia (aCML) is an infrequent chronic myeloproliferative disorder characterized by leukocytosis, absence of Philadelphia chromosome or BCR-ABL rearrangement, and marked myeloid dysplasia. Some cases have an absolute monocytosis but can be distinguished from chronic myelomonocytic leukemia (CMML) by the presence of a higher percentage (> 15%) of circulating immature granulocytes. PATIENTS AND METHODS: In a series of 11 patients with a diagnosis of aCML according to the FAB proposals we have analyzed the most relevant clinical, hematological and cytogenetic characteristics. RESULTS: The median age was 65 years (16-84). All but one case showed, at time of diagnosis, leukocytosis (median WBC was 36 x 10(9)/l), 55% had moderate anemia and 36% had thrombocytopenia. Most cases had marked dysplasia, particularly in the granulocytic lineage (82% of the cases), and all cases showed bone marrow red hypoplasia. Cytogenetic abnormalities were present in 9 out of the 11 patients. Trisomy 8 was observed in three cases and other clonal chromosomal abnormalities included deletions of 5q, 13q, 17p, 12q, and 11q as well as a t(6;8)(p23;q22) translocation. Fluorescence in situ hybridization (FISH) studies failed to demonstrate ETV-6 gene involvement. The median survival time from diagnosis was only 14 months (range 3-56 months). CONCLUSIONS: These data suggest that aCML is a rare disease which is characterized by leukocytosis, with dysgranulopoiesis, BM erythroid hypoplasia, chromosomal, though not recurrent, abnormalities and poor prognosis.

Adolescent↗
PubMed2000

Prolonged remission state of refractory adult onset Still's disease following CD34-selected autologous peripheral blood stem cell transplantation.

We report a 38-year-old patient affected by refractory adult onset Still's disease who achieved a prolonged remission following CD34-selected ABMT. The conditioning regimen was based on the use of CY and anti-thymocyte globulin. A 3.0 and 2.0 log reduction of T (CD3+) and B (CD19+) lymphocytes, respectively, was obtained using a Ceprate device to select CD34+ cells from PBSC. In the pre-transplant period (1994-1998) the patient had a chronic persistent disease course with frequent and recurrent systemic articular flares and loss of some functional abilities, despite daily prednisone, pulses of CY and immunosuppressive therapy (CYA or MTX). At the time of ABMT the patient had become non-ambulatory. Within 3 weeks of ABMT the patient showed a marked decrease in joint swelling, and morning stiffness. Joint pain and systemic symptoms disappeared, the patient was able to walk and run and gained general well being. ESR, C-reactive protein and WBC count were significantly decreased, while Hb level increased. This partial remission persisted for at least 1 year after ABMT, although at 15 months of follow-up a reappearance of moderate synovitis in the knees and wrists was noted. Our data further showed that both patient BM microenvironment and stem-progenitor cell function (as assessed by LTC-IC assay) were damaged even 1 year after CD34-selected ABMT, suggesting that the persistence of these alterations could have facilitated the favorable outcome of the disease following ABMT. Bone Marrow Transplantation (2000) 25, 1307-1310.

Adult↗
PubMed2000

Four novel non-random chromosome rearrangements in B-cell chronic lymphocytic leukaemia: 6p24-25 and 12p12-13 translocations, 4q21 anomalies and monosomy 21.

Nine patients with previously unreported chromosome changes were identified among 209 B-cell chronic lymphocytic leukaemia (CLL) cases: three patients had a translocation involving 6p24-25; three had a 12p12-13 translocation; two had 4q21 involvement (one with coexisting 6p anomaly); and two had monosomy 21. Interphase fluorescence in situ hybridization (FISH) detected some cryptic aberrations (+12, 6q-, 17p-, 11q-) in those patients with 6p translocations, whereas only a cytogenetically undetected 13q14 deletion was found in the remaining cases. Atypical morphology was noted in six cases, including both cases with monosomy 21, two cases with 6p and 4q21 anomaly and one case with 12p involvement. Four of these cases also had more than one phenotype deviation with respect to the classical CLL phenotype. Disease progression after 21-51 months (median 41) was noted in two cases with 6p and 4q21 involvement and in one case with 12p anomaly and monosomy 21. We arrived at the following conclusions: (i) 6p24-25 and, possibly, 4q21 lesions represent non-random events in CLL, occurring in association with other well-known unbalanced rearrangements; (ii) 12p rearrangements and monosomy 21 may possibly represent early chromosome defects that are not associated with the classical DNA gains and losses known to be present in the majority of CLL; and (iii) atypical morphology and immunophenotype as well as disease progression were frequently observed in these cases

Aged↗
PubMed2000

Acquired chromosome 11q deletion involving the ataxia teleangiectasia locus in B-cell non-Hodgkin's lymphoma: correlation with clinicobiologic features.

PURPOSE: To study the clinicobiologic significance of acquired 11q deletions involving the ataxia teleangiectasia locus (ATM+/-) in B-cell non-Hodgkin's lymphomas (NHL). PATIENTS AND METHODS: Fifty-three indolent lymphomas and 82 aggressive lymphomas were studied by conventional cytogenetic analysis and by fluorescence in situ hybridization using an 11q22-23 probe recognizing ATM sequences. Pertinent clinical data were collected. RESULTS: A hemizygous ATM deletion was seen in 44% to 88% of the interphase cells in 15 cases (11.1%); four patients had an indolent lymphoma (follicular center cell lymphoma), and 11 patients had an aggressive lymphoma (five mantle-cell lymphomas [MCLs] and six diffuse large-cell lymphomas). Dual-color hybridization studies showed ATM deletion to be possibly a secondary aberration in three patients with MCL. Ten out of 15 ATM+/- patients had a complex karyotype, 11 out of 15 had more than 90% abnormal metaphases (AA karyotype status), and +12, 13q14 deletion, and 17p13 deletion were seen in seven, four, and five cases, respectively. Patients with ATM+/- more frequently had a complex karyotype (P =.01) and the AA karyotype (P =.04) compared with patients without ATM+/-. With the exception of a poor performance status (P =.001), no correlation was found between ATM+/-, initial clinical variables, and complete remission rate; whereas a highly significant association was found with shorter survival (P <.0001). This cytogenetic lesion maintained its prognostic importance in multivariate analysis (P =.0004), along with performance status (P =.0006), serum lactate dehydrogenase level (P =.03), splenomegaly (P =.01), and histologic grade (P =.03). When analyzing indolent lymphomas and aggressive lymphomas separately, ATM+/- maintained its prognostic importance as an independent variable in both histologic groups (P =.0001 and P =.016, respectively). CONCLUSION: Though possibly not representing a primary genetic lesion in the majority of cases, the acquired ATM+/- status has clinicobiologic importance in NHL, possibly representing a major cytogenetic determinant of outcome.

Ataxia Telangiectasia↗
PubMed2000

Short-term analysis of the relationship between blood pressure and urinary sodium excretion in normotensive subjects.

The aim of this study was to investigate whether, in the short term, physiological blood pressure changes are coupled with changes in urinary sodium excretion in normotensive subjects, maintained at fixed sodium intake and under controlled postural and behavioural conditions. Twelve normotensive subjects were recruited. For each subject, seven urine samples were collected at fixed time intervals during an overall 26 h period: late afternoon (16.00-20.00 hours), evening (20.00-24.00 hours), night (24.00-06.00 hours), quiet wakefulness (06.00-09.00 hours), morning (09.00-12.00 hours), post-prandial (12.00-15.00 hours) and afternoon (15.00-18.00 hours). Blood pressure was monitored by an ambulatory blood pressure device during the whole 26 h period. Each urine sample was used to measure urinary sodium excretion and glomerular filtration rate (creatinine clearance). Blood pressure, heart rate, urinary sodium excretion and glomerular filtration rate recorded in the daytime were higher than those measured during the night-time. A significant positive correlation between mean blood pressure and urinary sodium excretion was found during the night, over the whole 26 h period, and during two subperiods of the daytime: quiet wakefulness and the post-prandial period. The coefficient of the pressure-natriuresis curve was significantly decreased by postural changes. We conclude that, in normotensive subjects, blood pressure and urinary sodium excretion are coupled in the short term. The assumption of an upright posture can mask this relationship, presumably by activating neurohumoral factors.

Adult↗
PubMed2000

Cytogenetic and molecular cytogenetic characterization of 6 new cases of idiopathic hypereosinophilic syndrome.

BACKGROUND AND OBJECTIVE: Idiopathic hypereosinophilic syndrome (HES) is defined as a peripheral blood eosiniphilia greater than 1, 500 cells/microL for longer than 6 months, absence of other apparent etiologies for eosinophilia and signs and symptoms of organ involvement. HES may be a reactive condition or a chronic myeloproliferative disorder but scanty information is available concerning its cytogenetic profile. DESIGN AND METHODS: Six patients with HES were studied by cytogenetic analysis. To increase the sensitivity of cytogenetic analysis, interphase FISH studies were performed to detect some cryptic chromosomal lesions involving the regions known to be frequently involved in myeloproliferative disorders (i.e. BCR/ABL, 5q31, 7q31.1, 11q23, 13q14, 17p13). Clinical parameters were recorded in all patients. RESULTS: A 3q deletion was detected in one patient; two unrelated clones with +14 and +11 were present in another patient who had a cryptic 5q31 deletion as disclosed by FISH; both patients had a mild clinical course. The 5q31 deletion was shown to involve the eosinophilic lineage and not the lymphoid cells. No chromosome abnormalities were found by karyotyping or interphase FISH in the remaining 4 cases. In two of these cases the clinical course was aggressive, with progressive leukocytosis and marked splenomegaly in one patient, central nervous system and cardiac involvement as well as bone marrow failure in the other. INTERPRETATION AND CONCLUSIONS: The 3q deletion, +11 and +14, and a cryptic 5q31 deletion involving the cells of the eosinophilic lineage are three novel chromosome abnormalities occurring in HES. We did not find a correlation between evolving or aggressive disease and the presence of chromosome anomalies. Our data confirm that HES is a clinically and biologically heterogeneous condition and suggest that more cases need to be studied to identify clinically significant chromosome changes in this rare condition. Some patients may benefit from treatment with interferon.

Adult↗
PubMed1999

Cytogenetic profile of lymphoma of follicle mantle lineage: correlation with clinicobiologic features.

Conventional chromosome analysis (CCA) and interphase fluorescence in situ hybridization (FISH) was performed in 42 patients with mantle-cell lymphoma (MCL), with BCL1 rearrangement. The t(11;14)(q13;q32) or 11q abnormalities were detected by CCA in 34 cases, 20 of which had additional aberrations. A normal karyotype was observed in 8 cases. Probes detecting the chromosome aberrations that were observed in at least 3 cases by CCA, ie, +12, 13q14 deletion, and 17p deletion, were used for interphase FISH analysis. FISH detected total or partial +12, 13q14 deletion and 17p- in 28.5%, 52.4%, and 26% of the cases, respectively. The presence of these anomalies was not a function of karyotype complexity. Based on the results of CCA/FISH, three groups of increasing karyotype complexity were recognized: group 1, including 11 patients without detectable aberrations in addition to BCL1 rearrangement; group 2, including 14 patients with 1 to 2 additional anomalies; and group 3, including 17 patients with three or more additional anomalies. Clinical parameters associated with shorter survival were male sex (P =.006) and primary lymph-node involvement compared with primary bone marrow involvement (P =.015). Trisomy 12 was the only single cytogenetic parameter predictive of a poor prognosis (P =.006) and the best prognostic indicator was the derived measure of karyotype complexity (P <.0001), which maintained statistical significance in multivariate analysis (P<.0001). We arrived at the following conclusions: 13q14 deletion occurs at a high incidence in MCL; 17p deletion and total/partial +12 are relatively frequent events in MCL, the latter aberration being associated with a shorter survival; and the degree of karyotype complexity has a strong impact on prognosis in this neoplasia.

Adult↗
PubMed1999

Therapy-related adult acute lymphoblastic leukemia with t(4;11)(q21; q23): MLL rearrangement, p53 mutation and multilineage involvement.

A diagnosis of pro-B acute lymphoblastic leukemia (ALL) with CD15+ was made in a 42-year-old woman, 12 months after the treatment of uterine adenocarcinoma by carboplatinum, anthracyclines, etoposide and radiotherapy. Molecular cytogenetic studies revealed a karyotype with multiple chromosome changes, including the t(4;11)(q21;q23) and a 17p-chromosome, with MLL disruption and 17p13/p53 gene deletion in 86% of the cells. A p53 exon 6 mutation was documented, resulting in p53 protein stabilization, with 20% of the cells reacting with the 1801 anti-p53 monoclonal antibody. Dual-color FISH using MLL and p53 probes was performed on peripheral blood smears, providing direct evidence of the involvement of the blast cells and of the granulocytic lineage. Only a partial, shortlasting response was obtained by induction treatment, confirming that a poor prognosis is associated with therapy-related ALL with the 4;11 translocation.

Adult↗
PubMed1999

Phenotypic and functional characteristics of monocyte-derived dendritic cells from patients with myelodysplastic syndromes.

We have compared the phenotypic and functional characteristics of dendritic cells (DC) generated in vitro from the peripheral blood mononuclear fraction of myelodysplastic syndrome (MDS) patients (four refractory anaemia, four refractory anaemia with excess of blasts) with DCs generated in a similar way from eight healthy donors. After 10 d of culture in the presence of GM-CSF and IL-4, reduced numbers and percentages of DCs were obtained in MDS subjects. MDS DCs exhibited significantly lower expression of CD1a, CD54, CD80 and MHC class II molecules. Their ability to stimulate T lymphocytes in an allogeneic mixed leucocyte reaction was reduced in comparison to normal subjects. Furthermore, MDS DCs also showed a reduced receptor-mediated endocytosis as demonstrated by FITC-dextran uptake. Simultaneous fluorescence in situ hybridization (FISH) and immunophenotypic analysis demonstrated that MDS DCs have the same cytogenetic abnormality of the malignant clone. Taken together these findings indicate that, in MDS, DCs are part of the malignant clone and exhibit a deficient antigen uptake and presentation.

Dendritic Cells↗
PubMed1999

13q14 deletion in non-Hodgkin's lymphoma: correlation with clinicopathologic features.

BACKGROUND AND OBJECTIVE: 13q14 deletion frequently occurs as a single anomaly in chronic lymphocytic leukemia (CLL) with favorable prognosis. This study was performed to assess the distribution of 13q14 deletion in non-Hodgkin's lymphoma (NHL) and to analyze its correlation with salient clinicopathologic features. DESIGN AND METHODS: One hundred and twenty-five NHL were analyzed by cytogenetics and by interphase fluorescence in situ hybridization (FISH), using a 13q14 cosmid probe recognizing DNA sequences between the Rb gene and the D13S25 marker. Clinical records all patients were surveyed. RESULTS: A 13q14 rearrangement was present in the stemline in 10 patients; 15 additional cases were shown by FISH to carry 13q14 deletion in 55-90% of the interphase cells, giving a 20% overall incidence for this anomaly. Six of 44 patients had a low-grade NHL, 14/28 had mantle cell lymphoma (MCL), 5/42 had a high grade NHL (p<0.0001). There was not correlation between 13q, karyotype status and complexity. A statistically significant association was found between 13q-, presence of splenomegaly and PB involvement, lower probability of attaining complete remission (CR) and shorter survival. These findings were not simply a function of the association of 13q- with MCL. In multivariate analysis, a complex karyotype had prognostic importance (p=0.0078), along with age (p=0.01), histology (p=0.001), LDH (p=0.03), PS (p=0.001), sex (p=0.03) and splenomegaly (p=0.02). INTERPRETATION AND CONCLUSIONS: 13q14 deletion represented an early chromosome change and showed a preferential association with MCL, though it was found in virtually all principal histologic subtypes, irrespective of clinical stage, karyotype status and complexity. Patients with 13q14 deletions had a low CR rate, suggesting that genes relevant to lymphomagenesis are located in this chromosome segment that warrants molecular cytogenetic investigation.

Biomarkers, Tumor↗