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

Mauvieux, Laurent; Canioni, Danielle; Hermine, Olivier; Valensi, Françoise; Radford‐Weiss, Isabelle; Azagury, M; Magen, Maryse; Flandrin, Georges; Brousse, Nicole; Varet, Bruno; Macintyre, Elisabeth

doi:10.1038/sj.leu.2400884

Cited by 16 publications

(12 citation statements)

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“…Application of cyclin D1 immunoperoxidase has been reported to be a useful and specific diagnostic adjunct in MCL (21,(37)(38)(39)(40)(41)(42)(43); however, in our experience, this method can be inconsistent, particularly in B5-fixed and decalcified tissues. Detection of cyclin D1 mRNA overexpression by slot blotting method (44) or RT-PCR technique as illustrated here and by others (45) may provide rapid, clinically useful alternatives. To this end, the determination of increased cyclin D1 levels by Western blot or molecular methods has been shown to identify prognostically relevant patient groups among some chronic B-cell leukemias, despite the difficulty in accurately classifying many of these neoplasms by cytomorphologic criteria (46).…”

Section: Discussionmentioning

confidence: 93%

Blastic Mantle Cell Leukemia: An Unusual Presentation of Blastic Mantle Cell Lymphoma

et al. 2000

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Six patients had blood and bone marrow manifestations characterized by the presence of morphologically immature or blastic B-lineage lymphoid cells expressing CD5 antigen. The median patient age was 70 years, and the male-to-female ratio was 5:1. The presence or degree of lymphadenopathy and splenomegaly was variable among this group at staging evaluation, although two patients did not have these features. One patient had an antecedent diagnosis of classical nodal mantle cell lymphoma, without prior morphologic blood or bone marrow involvement. Other patients lacked a history of underlying lymphoproliferative disorders. The median white blood cell count was 120 ؋ 10 9 /L. Most patients had thrombocytopenia, whereas only one patient had neutropenia at presentation. Leukemic peripheral blood cells in these six cases were small to medium in size with fine or granular nuclear chromatin and small or inconspicuous nucleoli. The pattern of marrow involvement was interstitial or diffuse, with cells showing immature nuclear features resembling acute leukemia or blastic lymphoma. All tumors demonstrated a consistent immunophenotype of B-cell lineage, surface immunoglobulin positivity, and CD5 antigen expression. The progenitor cell-associated markers CD34 and TdT were not expressed, and CD23 antigen was either negative (three of four cases) or only weakly present (one of four cases). The presence of a karyotypic t(11;14)(q13;q32) was documented in one tumor, whereas two other cases had BCL-1 gene rearrangements by either polymerase chain reaction or Southern blot analysis. Cyclin D1 mRNA overexpression was noted in three of four cases tested. This patient group was characterized by very poor overall survival (median, 3 months; range, 0.5 to 6 months). The aggregate clinical, pathologic, and genetic data in these unusual cases are consistent with de novo or predominant leukemic presentations of blastic mantle cell lymphoma. Accurate diagnosis in such cases is greatly facilitated by cytogenetic studies or the demonstration of BCL-1/ cyclin D1 abnormalities. The expression of surface immunoglobulin (SIg) generally signifies a mature B-cell phenotype and is usually accompanied by nuclear changes of chromatin condensation. However, exceptional lymphoid neoplasms characterized by blastic cytology and mature phenotype have been described. One example is a previous report of nine cases of "mature" B-cell acute lymphoblastic leukemia (ALL), characterized by non-L3 leukemic blast morphology and the presence of SIg positivity (1). These cases were phenotypically somewhat heterogeneous, although TdT was consistently negative in each case and CD10 expression was observed in all of five tumors tested for this antigen. Among these unusual blastic, SIg-positive leukemic cases, karyotypic analysis also revealed heterogeneity. Two tumors exhibited 8(q24) region translocations, implying C-MYC gene deregulation. Of interest, one of these lesions had a t(14;18) anomaly, in addition to 8(q24) rearrangement, suggesting blastic transformation of...

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Section: Discussionmentioning

confidence: 93%

Blastic Mantle Cell Leukemia: An Unusual Presentation of Blastic Mantle Cell Lymphoma

et al. 2000

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“…11 (2) Bcll gene rearrangement using PCR was found in two cases. 12 (3) Using RT-PCR or the slot-blot technique, 13,14 cyclin D1 overexpression was detected in 15 cases.…”

Section: Molecular Study and Cytogenetic Analysismentioning

confidence: 99%

Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype

Bernard¹,

et al. 2001

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The blastic variant (BV) form of mantle cell lymphoma (MCL) is considered to be a very aggressive subtype of non-Hodgkin's lymphoma (NHL). In order to determine its clinico-biological features and response to therapy we studied 33 patients (17%) out of 187 suffering from MCL who were diagnosed with a BV of MCL. Blastic variant was diagnosed according to histopathological patterns, immunophenotyping, and bcl1 gene rearrangement and/or cyclin D1 overexpression. Three patients initially diagnosed with large cell NHL were classified as BV. Patients received front-line therapy including CHOP-like regimen or CVP (n = 29), or chlorambucil (n = 4) and CHOP or ESAP as second-line therapy. High-dose intensification with stem cell transplantation (SCT) was performed in 11 cases (autoSCT, n = 8; alloSCT, n = 3). All but two patients were in complete remission (CR) at the time of transplant (CR1, n = 5; CR2, n = 4). Clinical and biological characteristics did not differ from those of the common form of MCL. The median age was 62 years (29-80), with a sex ratio (M/F) of 2.6:1. Of the 33 patients, 66% had extranodal site involvement, 85% had an Ann Arbor stage IV, and 82% had peripheral lymphadenopathy. Circulating lymphomatous cells were seen in 48% of cases. Twelve patients (36%) entered a CR1 with a median duration of 11 months. Fifteen patients (46%) failed to respond and rapidly died of progressive disease. Second-line therapy led to a 26% (6/23) CR2 rate. Nine patients relapsed after high-dose therapy. Twenty-two of the 33 patients (66%) died of refractory or progressive disease. Median overall survival (OS) time was 14.5 months for the 33 BV patients as compared to 53 months for the 154 patients with a common form of MCL, P Ͻ0.0001. In the univariate analysis, OS was influenced by age, extranodal site involvement, circulating lymphomatous cells, and international prognosis index (IPI). In the multivariate analysis, only IPI affected OS: patients with IPI у2 had 8 months median OS as compared to 36 months median OS for patients with IPI Ͻ2, P = 0.003. Blastic variant is one of the worst forms of NHL. An improved recognition of BV of MCL is required, particularly in high-grade CD5 + NHL using immunophenotyping and bcl1 molecular study. Standard therapy using anthracycline or even high-dose intensification produce poor results and an alternative treatment should be proposed to such patients. Leukemia (2001) 15, 1785-1791.

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“…The diagnosis was based on a combination of morphologic, immunologic, cytogenetic and molecular criteria as previously described. 2,7,8,14,17 Patients with mantle zone pattern, which is associated with a favorable course, were excluded from the study. 18 All cases were reviewed by expert hematopathologists for confirmation of diagnosis.…”

Section: Leukemiamentioning

confidence: 99%

“…7,17 Cytogenetic analysis, cyclin D1 mRNA expression and IgH/Bc11 translocation were performed when fresh or cryopreserved material was available as described earlier. 6,7 Patients with any of the following were ineligible: cardiac ejection fraction less than 50%, insufficient pulmonary function, severe renal or hepatic function impairment.…”

Section: Leukemiamentioning

confidence: 99%

“…MCL is frequently associated with the t(11;14) translocation, which results in the overexpression of cyclin D1 gene within the bcl-1 locus. 3,[4][5][6][7] Despite an initial relatively indolent clinical presentation, the prognosis of MCL remains poor with a median survival time of less than 3 years. 3,[8][9][10][11] Adverse prognostic factors such as poor performance status (PS), B symptoms, high LDH and ␤2-microglobulin levels are observed in more than 50% of patients during the progression of the disease.…”

Section: Introductionmentioning

confidence: 99%

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Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study

et al. 2002

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Mantle cell lymphoma (MCL) is a distinct clinico-pathological entity with a poor prognosis. We have conducted a prospective study in patients with MCL to evaluate a therapeutic strategy in which CHOP polychemotherapy was followed by DHAP if CHOP failed to induce complete remission. Responding patients then proceeded to an intensification therapy with autologous peripheral blood stem cell transplantation (APBSCT). Twenty-eight consecutive patients with newly diagnosed aggressive MCL were included. After four cycles of CHOP regimen, two complete responses (CR) were obtained (7%) and 14 (50%), five (18%) and seven (25%) patients achieved partial (PR), minor (MR) and no response, respectively (one patient died from septic complications during CHOP induction). The two patients in CR after CHOP underwent intensification with TBI, high-dose cyclophosphamide-etoposide and APBSCT. The other twentyfive patients received DHAP and in this group a response rate of 92% (21 CR (84%), two PR (8%)) was observed. Two patients had progressive disease. The twenty-three responding patients received high-dose therapy (TAM8 regimen: TBI-cytarabinemelphalan) followed by APBSCT. One of the two partial responding patients achieved CR after TAM8. After a median follow-up of 47.6 months (range, 14-70), seven patients have relapsed. Our data confirm that: (1) CHOP regimen induces a low CR rate in MCL; (2) CHOP plus DHAP appears to be much more efficient and allows a large proportion of patients to proceed to high-dose therapy in CR; (3) consolidation therapy including TBI and high-dose Arac-C followed by APBSCT may improve event-free survival.

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

Cited by 16 publications

References 3 publications

Blastic Mantle Cell Leukemia: An Unusual Presentation of Blastic Mantle Cell Lymphoma

Blastic Mantle Cell Leukemia: An Unusual Presentation of Blastic Mantle Cell Lymphoma

Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype

Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study

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