Contributions
Abstract: PB2333
Type: Publication Only
Background
Immunoglobulin heavy chain V-gene (IGHV) mutational status is known to be a key factor for the long-term prognosis in B-cell chronic lymphocytic leukemia (B-CLL). In addition, the diversity of rearranged IGHV genes in B-CLL cells is very limited and significantly different from that of normal B cells. Recent data obtained suggest narrowing of the IGHV repertoire not only in B-CLL but also in other B-cell lymphomas (such as hairy cell leukemia, marginal zone lymphoma, etc.).
Aims
To compare the sequences of IGHV genes in patients with various B-cell malignancies.
Methods
The study included 790 patients with B-CLL, 45 with splenic marginal zone lymphoma (SMZL) and 33 with hairy cell leukemia (HCL). Rearranged IGHV genes for 683 patients observed at the National Research Center for Hematology (2006-2017) and for 185 patients observed at Almazov North-West Federal Medical Research Center (2012-2016) were sequenced according to Sanger procedure and analyzed as described in [Biderman et al., 2012].
Results
Rearranged IGHV gene repertoire for B-cell malignancies was compared. V-gene family usage was different for B-CLL, HCL and SMZL. For example, VH3 genes are most often (60%) expressed in HCL, VH4 and VH1 genes are less common - 21% and 12%, respectively. In SMZL, half of all cases represent VH1 genes (51%), 27% - VH3 genes and 15% - VH4. In the case of B-CLL, 45% are VH3, 30% and 17.5% are VH1 and VH4 respectively. While typical distribution for normal B cells is VH3 - 57%, VH1 - 20%, VH4 - 18% [Fais et al., 1998]. Other VH genes usage was also rare for the cases investigated (1% -2%), similar to that for normal B cells. For SMZL patients from our sample with VH1 family genes all cases (with the exception of one) represent IGHV1-2 gene (49% of the total sample). In addition, there is a very high similarity of the nucleotide sequences of the CDR3 region for several of these cases (Pic. 1). On the other hand, in B-CLL this gene is relatively rare and occurs in 5% of cases. Furthermore in B-CLL this gene is preferably unmutated (84%), while in SMZL the frequencies of mutated and unmutated cases are similar. It should be noted that IGHV1-2 gene usage was not detected for HCL patients in our sample. In B-CLL, the most common gene was IGHV1-69 (18%), it also participates in the formation of the most common stereotypic antigenic receptors (CLL # 3, 5, 6). Two cases (6%) with IGHV1-69 gene usage were detected in HCL patients, and none in SMZL patients. No stereotypic antigenic receptors described for B-CLL so far were found in our sample of SMZL and HCL patients.
Conclusion
The narrowing of the IGHV gene repertoire in B-CLL, HCL and SMZL suggests antigen stimulation of B-cells could play an important role in the development of these diseases. At the same time differences in IGHV gene repertoire between these B-cell malignancies may indicate that different antigens may be involved. Unfortunately, our sample of patients with SMZL and HCL are much smaller than that for B-CLL. Further studies with extended samples of SMZL and HCL may be beneficial to reveal possible prognostic factors and probably CDR3 stereotype data for these diseases.
Session topic: 19. Non-Hodgkin lymphoma Biology & Translational Research
Keyword(s): Chronic Lymphocytic Leukemia, Hairy cell leukemia, IgH rearrangment, Splenic marginal zone lymphoma
Abstract: PB2333
Type: Publication Only
Background
Immunoglobulin heavy chain V-gene (IGHV) mutational status is known to be a key factor for the long-term prognosis in B-cell chronic lymphocytic leukemia (B-CLL). In addition, the diversity of rearranged IGHV genes in B-CLL cells is very limited and significantly different from that of normal B cells. Recent data obtained suggest narrowing of the IGHV repertoire not only in B-CLL but also in other B-cell lymphomas (such as hairy cell leukemia, marginal zone lymphoma, etc.).
Aims
To compare the sequences of IGHV genes in patients with various B-cell malignancies.
Methods
The study included 790 patients with B-CLL, 45 with splenic marginal zone lymphoma (SMZL) and 33 with hairy cell leukemia (HCL). Rearranged IGHV genes for 683 patients observed at the National Research Center for Hematology (2006-2017) and for 185 patients observed at Almazov North-West Federal Medical Research Center (2012-2016) were sequenced according to Sanger procedure and analyzed as described in [Biderman et al., 2012].
Results
Rearranged IGHV gene repertoire for B-cell malignancies was compared. V-gene family usage was different for B-CLL, HCL and SMZL. For example, VH3 genes are most often (60%) expressed in HCL, VH4 and VH1 genes are less common - 21% and 12%, respectively. In SMZL, half of all cases represent VH1 genes (51%), 27% - VH3 genes and 15% - VH4. In the case of B-CLL, 45% are VH3, 30% and 17.5% are VH1 and VH4 respectively. While typical distribution for normal B cells is VH3 - 57%, VH1 - 20%, VH4 - 18% [Fais et al., 1998]. Other VH genes usage was also rare for the cases investigated (1% -2%), similar to that for normal B cells. For SMZL patients from our sample with VH1 family genes all cases (with the exception of one) represent IGHV1-2 gene (49% of the total sample). In addition, there is a very high similarity of the nucleotide sequences of the CDR3 region for several of these cases (Pic. 1). On the other hand, in B-CLL this gene is relatively rare and occurs in 5% of cases. Furthermore in B-CLL this gene is preferably unmutated (84%), while in SMZL the frequencies of mutated and unmutated cases are similar. It should be noted that IGHV1-2 gene usage was not detected for HCL patients in our sample. In B-CLL, the most common gene was IGHV1-69 (18%), it also participates in the formation of the most common stereotypic antigenic receptors (CLL # 3, 5, 6). Two cases (6%) with IGHV1-69 gene usage were detected in HCL patients, and none in SMZL patients. No stereotypic antigenic receptors described for B-CLL so far were found in our sample of SMZL and HCL patients.
Conclusion
The narrowing of the IGHV gene repertoire in B-CLL, HCL and SMZL suggests antigen stimulation of B-cells could play an important role in the development of these diseases. At the same time differences in IGHV gene repertoire between these B-cell malignancies may indicate that different antigens may be involved. Unfortunately, our sample of patients with SMZL and HCL are much smaller than that for B-CLL. Further studies with extended samples of SMZL and HCL may be beneficial to reveal possible prognostic factors and probably CDR3 stereotype data for these diseases.
Session topic: 19. Non-Hodgkin lymphoma Biology & Translational Research
Keyword(s): Chronic Lymphocytic Leukemia, Hairy cell leukemia, IgH rearrangment, Splenic marginal zone lymphoma