Genetic alterations in B-cell non-Hodgkin's lymphoma

Background. Although the patients with diagnosed B-NHL are classified into the same disease stage on the basis of clinical, histopathological, and immunological parameters, they respond significantly different to the applied treatment. This points out the possibility that within the same group of ly...

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Main Authors: Magić Zvonko, Novković Tamara, Cikota Bojana, Tasić-Radić Olga, Tarabar Olivera, Stamatović Dragana
Format: Article
Language:English
Published: Ministry of Defence of the Republic of Serbia, University of Defence, Belgrade 2005-01-01
Series:Vojnosanitetski Pregled
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Online Access:http://www.doiserbia.nb.rs/img/doi/0042-8450/2005/0042-84500502087M.pdf
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author Magić Zvonko
Novković Tamara
Cikota Bojana
Tasić-Radić Olga
Tarabar Olivera
Stamatović Dragana
author_facet Magić Zvonko
Novković Tamara
Cikota Bojana
Tasić-Radić Olga
Tarabar Olivera
Stamatović Dragana
author_sort Magić Zvonko
collection DOAJ
description Background. Although the patients with diagnosed B-NHL are classified into the same disease stage on the basis of clinical, histopathological, and immunological parameters, they respond significantly different to the applied treatment. This points out the possibility that within the same group of lymphoma there are different diseases at molecular level. For that reason many studies deal with the detection of gene alterations in lymphomas to provide a better framework for diagnosis and treatment of these hematological malignancies. Aim. To define genetic alterations in the B-NHL with highest possibilities for diagnostic purposes and molecular detection of MRD. Methods. Formalin fixed and paraffin embedded lymph node tissues from 45 patients were examined by different PCR techniques for the presence of IgH and TCR γ gene rearrangement; K-ras and H-ras mutations; c-myc amplification and bcl-2 translocation. There were 34 cases of B-cell non-Hodgkin’s lymphoma (B-NHL), 5 cases of T-cell non-Hodgkin’s lymphoma (T-NHL) and 6 cases of chronic lymphadenitis (CL). The mononuclear cell fraction of the peripheral blood of 12 patients with B-NHL was analyzed for the presence of monoclonality at the time of diagnosis and in 3 to 6 months time intervals after an autologous bone marrow transplantation (BMT). Results. The monoclonality of B-lymphocytes, as evidenced by DNA fragment length homogeneity, was detected in 88 % (30/34) of B-NHL, but never in CL, T-NHL, or in normal PBL. Bcl-2 translocation was detected in 7/31 (22.6%) B-NHL specimens, c-myc amplification 9/31 (29%, all were more than doubled), K-ras mutations in 1/31 (3.23%) and H-ras mutations in 2/31 (6.45%) of the examined B-NHL samples. In the case of LC and normal PBL, however, these gene alterations were not detected. All the patients (12) with B-NHL had dominant clone of B-lymphocyte in the peripheral blood at the time of diagnosis while only in 2 of 12 patients MRD was detected 3 or 6 months after BMT. Conclusion. Because it is quick and simple, PCR analysis of clonal IgH rearrangements is very useful when diagnostic assistance is required. This technique is also very efficient for tracking minimal residual disease in lymphomas and leukemia's and for monitoring clonal evolution in acute and chronic lymphoblastic leukemia's and lymphomas. The presence of other genetic alterations, which we detected, should serve as an additional prognostic or predictive factor in the patients with B-NHL.
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spelling doaj-art-3ebdfddc862c4d9cbec983c355d75b652025-08-20T01:56:25ZengMinistry of Defence of the Republic of Serbia, University of Defence, BelgradeVojnosanitetski Pregled0042-84502005-01-01622879610.2298/VSP0502087MGenetic alterations in B-cell non-Hodgkin's lymphomaMagić ZvonkoNovković TamaraCikota BojanaTasić-Radić OlgaTarabar OliveraStamatović DraganaBackground. Although the patients with diagnosed B-NHL are classified into the same disease stage on the basis of clinical, histopathological, and immunological parameters, they respond significantly different to the applied treatment. This points out the possibility that within the same group of lymphoma there are different diseases at molecular level. For that reason many studies deal with the detection of gene alterations in lymphomas to provide a better framework for diagnosis and treatment of these hematological malignancies. Aim. To define genetic alterations in the B-NHL with highest possibilities for diagnostic purposes and molecular detection of MRD. Methods. Formalin fixed and paraffin embedded lymph node tissues from 45 patients were examined by different PCR techniques for the presence of IgH and TCR γ gene rearrangement; K-ras and H-ras mutations; c-myc amplification and bcl-2 translocation. There were 34 cases of B-cell non-Hodgkin’s lymphoma (B-NHL), 5 cases of T-cell non-Hodgkin’s lymphoma (T-NHL) and 6 cases of chronic lymphadenitis (CL). The mononuclear cell fraction of the peripheral blood of 12 patients with B-NHL was analyzed for the presence of monoclonality at the time of diagnosis and in 3 to 6 months time intervals after an autologous bone marrow transplantation (BMT). Results. The monoclonality of B-lymphocytes, as evidenced by DNA fragment length homogeneity, was detected in 88 % (30/34) of B-NHL, but never in CL, T-NHL, or in normal PBL. Bcl-2 translocation was detected in 7/31 (22.6%) B-NHL specimens, c-myc amplification 9/31 (29%, all were more than doubled), K-ras mutations in 1/31 (3.23%) and H-ras mutations in 2/31 (6.45%) of the examined B-NHL samples. In the case of LC and normal PBL, however, these gene alterations were not detected. All the patients (12) with B-NHL had dominant clone of B-lymphocyte in the peripheral blood at the time of diagnosis while only in 2 of 12 patients MRD was detected 3 or 6 months after BMT. Conclusion. Because it is quick and simple, PCR analysis of clonal IgH rearrangements is very useful when diagnostic assistance is required. This technique is also very efficient for tracking minimal residual disease in lymphomas and leukemia's and for monitoring clonal evolution in acute and chronic lymphoblastic leukemia's and lymphomas. The presence of other genetic alterations, which we detected, should serve as an additional prognostic or predictive factor in the patients with B-NHL.http://www.doiserbia.nb.rs/img/doi/0042-8450/2005/0042-84500502087M.pdflymphomanon-Hodgkingenetic phenomenamutationpolymerase chain reaction
spellingShingle Magić Zvonko
Novković Tamara
Cikota Bojana
Tasić-Radić Olga
Tarabar Olivera
Stamatović Dragana
Genetic alterations in B-cell non-Hodgkin's lymphoma
Vojnosanitetski Pregled
lymphoma
non-Hodgkin
genetic phenomena
mutation
polymerase chain reaction
title Genetic alterations in B-cell non-Hodgkin's lymphoma
title_full Genetic alterations in B-cell non-Hodgkin's lymphoma
title_fullStr Genetic alterations in B-cell non-Hodgkin's lymphoma
title_full_unstemmed Genetic alterations in B-cell non-Hodgkin's lymphoma
title_short Genetic alterations in B-cell non-Hodgkin's lymphoma
title_sort genetic alterations in b cell non hodgkin s lymphoma
topic lymphoma
non-Hodgkin
genetic phenomena
mutation
polymerase chain reaction
url http://www.doiserbia.nb.rs/img/doi/0042-8450/2005/0042-84500502087M.pdf
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AT cikotabojana geneticalterationsinbcellnonhodgkinslymphoma
AT tasicradicolga geneticalterationsinbcellnonhodgkinslymphoma
AT tarabarolivera geneticalterationsinbcellnonhodgkinslymphoma
AT stamatovicdragana geneticalterationsinbcellnonhodgkinslymphoma