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IGVH SOMATIC MUTATION PROFILE AS PATHOGENETIC SIGNATURE IN SPLENIC MARGINAL ZONE LYMPHOMA AND SPLENIC DIFFUSE RED PULP LYMPHOMA
Author(s):
Hunan L Julhakyan
,
Hunan L Julhakyan
Affiliations:
National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation,Moscow, Russian Federation
B. Biderman
,
B. Biderman
Affiliations:
National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation,Moscow, Russian Federation
L. Al-Radi
,
L. Al-Radi
Affiliations:
National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation,Moscow, Russian Federation
I. Yakutik
,
I. Yakutik
Affiliations:
National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation,Moscow, Russian Federation
S. Korzhova
,
S. Korzhova
Affiliations:
National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation,Moscow, Russian Federation
A. Kovrigina
,
A. Kovrigina
Affiliations:
National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation,Moscow, Russian Federation
A. Sudarikov
,
A. Sudarikov
Affiliations:
National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation,Moscow, Russian Federation
V. Savchenko
V. Savchenko
Affiliations:
National Research Center for Hematology of the Ministry of Healthcare of the Russian Federation,Moscow, Russian Federation
(Abstract release date: 05/18/17) EHA Library. Julhakyan H. 05/18/17; 182785; PB2071
Dr. Hunan Julhakyan
Dr. Hunan Julhakyan
Contributions
PDF Abstract
Abstract

Abstract: PB2071

Type: Publication Only

Background

Splenic lymphomas (SLs) are rare chronic lymphoproliferative neoplasms with a very indolent clinical course and a non-characteristic phenotype and karyotype. Splenic marginal zone lymphoma (SMZL), a specific type of small B-cell lymphoma and characterized by a peculiar morphology with micronodular pattern of infiltration, biphasic cytology, and the almost constant presence of marginal zone differentiation. Splenic diffuse red pulp lymphoma been introduced as a provisional entity but differential diagnosis with other SLs is needed to be clarified since the therapeutic approaches are distrinct.

Aims
The aim of our study to determine the immunoglobulin variable heavy chain (IgVH) gene usage and somatic mutation patterns in a series of SMZL and SDRP patients.

Methods

We studied 24 patients with SMZL, 40 patients with HCL and 10 patients with SDRPL. Diagnosis was based on standard WHO criteria. In all patients, the diagnosis was based on peripheral blood and BM findings. The baseline clinical and laboratory features as well as follow-up and outcome were recorded for every patient. Rearranged IgVH genes were amplified essentially in reactions that contained only one of the 5’ leader region primers for the indicated 6 VH families and a 3’J primer. All PCR reactions were performed using appropriate positive and negative controls. The rearranged VH genes identified for each case seemed to represent functional rearrangements because no stop codons or crippling mutations were identified.

Results
A comparison of the VH genes to reported germline sequences in SMZL revealed that 6 cases used the VH3 family VH gene segments, 2 the VH4 family, 16 the VH1 family segments. The VH1 family genes V1-2 were used in 16 cases. In 4 out of 24 cases (16.67%), IgVH genes were in germline or near germline configuration, whereas in 20 cases (83.33%), IgVH genes were somatically mutated. We have shown no differences in clinical and laboratory characteristics, immunophenotype, outcome or overall survival were found between the mutated and unmutated cases of SMZL. A comparison of the VH genes to reported germline sequences in SDRPL revealed that five cases used the VH3 family VH gene segments and five the VH4 family, one of case with unmutaited IgVH genes.

Conclusion
Our analysis also showed the selective use of VH1 family genes in a high proportion of SMZL cases (66.67%), while VH4 and VH3 family genes were represented at a lower frequency (8.33% and 25%, respectively). The present study may revealed that SMZL and SDRPL derive from different cellular origin and may use in differential diagnosis.

Session topic: 18. Non-Hodgkin & Hodgkin lymphoma - Biology

Keyword(s): Splenic marginal zone lymphoma, Mutation status, mutation analysis, VH gene

Abstract: PB2071

Type: Publication Only

Background

Splenic lymphomas (SLs) are rare chronic lymphoproliferative neoplasms with a very indolent clinical course and a non-characteristic phenotype and karyotype. Splenic marginal zone lymphoma (SMZL), a specific type of small B-cell lymphoma and characterized by a peculiar morphology with micronodular pattern of infiltration, biphasic cytology, and the almost constant presence of marginal zone differentiation. Splenic diffuse red pulp lymphoma been introduced as a provisional entity but differential diagnosis with other SLs is needed to be clarified since the therapeutic approaches are distrinct.

Aims
The aim of our study to determine the immunoglobulin variable heavy chain (IgVH) gene usage and somatic mutation patterns in a series of SMZL and SDRP patients.

Methods

We studied 24 patients with SMZL, 40 patients with HCL and 10 patients with SDRPL. Diagnosis was based on standard WHO criteria. In all patients, the diagnosis was based on peripheral blood and BM findings. The baseline clinical and laboratory features as well as follow-up and outcome were recorded for every patient. Rearranged IgVH genes were amplified essentially in reactions that contained only one of the 5’ leader region primers for the indicated 6 VH families and a 3’J primer. All PCR reactions were performed using appropriate positive and negative controls. The rearranged VH genes identified for each case seemed to represent functional rearrangements because no stop codons or crippling mutations were identified.

Results
A comparison of the VH genes to reported germline sequences in SMZL revealed that 6 cases used the VH3 family VH gene segments, 2 the VH4 family, 16 the VH1 family segments. The VH1 family genes V1-2 were used in 16 cases. In 4 out of 24 cases (16.67%), IgVH genes were in germline or near germline configuration, whereas in 20 cases (83.33%), IgVH genes were somatically mutated. We have shown no differences in clinical and laboratory characteristics, immunophenotype, outcome or overall survival were found between the mutated and unmutated cases of SMZL. A comparison of the VH genes to reported germline sequences in SDRPL revealed that five cases used the VH3 family VH gene segments and five the VH4 family, one of case with unmutaited IgVH genes.

Conclusion
Our analysis also showed the selective use of VH1 family genes in a high proportion of SMZL cases (66.67%), while VH4 and VH3 family genes were represented at a lower frequency (8.33% and 25%, respectively). The present study may revealed that SMZL and SDRPL derive from different cellular origin and may use in differential diagnosis.

Session topic: 18. Non-Hodgkin & Hodgkin lymphoma - Biology

Keyword(s): Splenic marginal zone lymphoma, Mutation status, mutation analysis, VH gene

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