Contributions
Abstract: EP615
Type: E-Poster Presentation
Session title: Chronic lymphocytic leukemia and related disorders - Biology & Translational Research
Background
Unmutated (UM) immunoglobulin heavy chain variable region (IgHV) status or subset #2 stereotyped Ig receptor (IgHV3-21/IgLV3-21) expression is associated with poor prognosis in chronic lymphocytic leukemia (CLL). It is considered that the light chain also can affect CLL outcome. The IgLV3-21 light chain usage was shown to confer unfavourable prognosis irrespective of IgHV mutational status or subset #2 stereotyped receptor.
Aims
To analyse the presence of IgLV3-21 in CLL cohort and corelate it with clinical outcome and poor prognosis molecular markers.
Methods
A total of 166 CLL patients with available IgHV data and clinico-biological information were included in the study. All patients gave written informed consent. Patient characteristics were as follows: 72% males; median age: 57; Binet stages B or C: 55%; IgHV status: 73% IgHV-unmutated (more or equal 98% identity to germline, UM); 27% IgHV-mutated (less than 98% germline identity, M), recurrent mutations: TP53: 12.9% (13 of 101 cases), NOTCH1: 10.3% (15 of 145 cases); SF3B1: 18.3% (17 of 93 cases); major stereotyped subsets assigned using the ARResT/AssignSubsets tool: 20.5%, the most frequent: subset #1 (4.2 %), subset #2 (3.0%), subset #3 (2.4%), subset #6 (2.4%). In 115 patients the Ig light chain rearrangements were analysed by Sanger sequencing using BIOMED-2 protocol, in 51 patients the IgLV3-21 chain presence was tested with real-time PCR method and primer strategy developed by Stamatopoulos et al. [2018]. Time-to-first-treatment (TTFT) and overall survival (OS) were analyzed by Kaplan-Meier statistic.
Results
The IgLV3-21 light chain expression was found in 16 (9.6%) patients in studied group, among them 5 cases (31.3%) belonged to subset #2 (IgHV3-21/IgLV3-21). Non-subset #2 IgHV3-21 cases were not represented. Besides of stereotyped subset #2, only subset #5 was represented (one case). More than half of the IgLV3-21 expressing cases (9 of 16) were IgHV M, largely due to subset #2 cases, all of which were IgHV M. In accordance with previous studies a higher frequency of SF3B1 mutations was seen in IgLV3-21 patients (P = 0.061), they were presented irrespective of subset #2 stereotyped Ig expression (subset #2: 50% and non-subset #2: 33.3%, P = 0.548). At that, SF3B1 mutations did not affect significantly neither OS (P = 0.525), nor TTFT (P = 0.831). Patients with the IgLV3-21 chain demonstrated a significantly shorter median OS compared to IgHV M (70 vs. 277 months, P = 0.005), but comparable to IgHV UM cases (75 months, P = 0.688). Similarly, TTFT was shorter in IgLV3-21 compared to IgHV M cases, although did not reach statistical significance (15 vs. 33 months, P = 0.161), and did not differ significantly from IgHV UM cases (8 months, P = 0.255). Upon dividing IgLV3-21 group into subset #2, non-subset #2/IgHV M and IgHV UM, we did not find a significant difference regarding both OS (P = 0.714) and TTFT (P = 0.259).
Conclusion
Our results in line with previous publications suggest that the IgLV3-21 light chain expression identifies unfavourable CLL subgroup independent of the IgHV mutational status and is associated with presence of SF3B1 mutations. Subsequent studies in a larger CLL cohort will clarify the significance of IgLV3-21 for risk stratification of patients.
Keyword(s): Chronic lymphocytic leukemia
Abstract: EP615
Type: E-Poster Presentation
Session title: Chronic lymphocytic leukemia and related disorders - Biology & Translational Research
Background
Unmutated (UM) immunoglobulin heavy chain variable region (IgHV) status or subset #2 stereotyped Ig receptor (IgHV3-21/IgLV3-21) expression is associated with poor prognosis in chronic lymphocytic leukemia (CLL). It is considered that the light chain also can affect CLL outcome. The IgLV3-21 light chain usage was shown to confer unfavourable prognosis irrespective of IgHV mutational status or subset #2 stereotyped receptor.
Aims
To analyse the presence of IgLV3-21 in CLL cohort and corelate it with clinical outcome and poor prognosis molecular markers.
Methods
A total of 166 CLL patients with available IgHV data and clinico-biological information were included in the study. All patients gave written informed consent. Patient characteristics were as follows: 72% males; median age: 57; Binet stages B or C: 55%; IgHV status: 73% IgHV-unmutated (more or equal 98% identity to germline, UM); 27% IgHV-mutated (less than 98% germline identity, M), recurrent mutations: TP53: 12.9% (13 of 101 cases), NOTCH1: 10.3% (15 of 145 cases); SF3B1: 18.3% (17 of 93 cases); major stereotyped subsets assigned using the ARResT/AssignSubsets tool: 20.5%, the most frequent: subset #1 (4.2 %), subset #2 (3.0%), subset #3 (2.4%), subset #6 (2.4%). In 115 patients the Ig light chain rearrangements were analysed by Sanger sequencing using BIOMED-2 protocol, in 51 patients the IgLV3-21 chain presence was tested with real-time PCR method and primer strategy developed by Stamatopoulos et al. [2018]. Time-to-first-treatment (TTFT) and overall survival (OS) were analyzed by Kaplan-Meier statistic.
Results
The IgLV3-21 light chain expression was found in 16 (9.6%) patients in studied group, among them 5 cases (31.3%) belonged to subset #2 (IgHV3-21/IgLV3-21). Non-subset #2 IgHV3-21 cases were not represented. Besides of stereotyped subset #2, only subset #5 was represented (one case). More than half of the IgLV3-21 expressing cases (9 of 16) were IgHV M, largely due to subset #2 cases, all of which were IgHV M. In accordance with previous studies a higher frequency of SF3B1 mutations was seen in IgLV3-21 patients (P = 0.061), they were presented irrespective of subset #2 stereotyped Ig expression (subset #2: 50% and non-subset #2: 33.3%, P = 0.548). At that, SF3B1 mutations did not affect significantly neither OS (P = 0.525), nor TTFT (P = 0.831). Patients with the IgLV3-21 chain demonstrated a significantly shorter median OS compared to IgHV M (70 vs. 277 months, P = 0.005), but comparable to IgHV UM cases (75 months, P = 0.688). Similarly, TTFT was shorter in IgLV3-21 compared to IgHV M cases, although did not reach statistical significance (15 vs. 33 months, P = 0.161), and did not differ significantly from IgHV UM cases (8 months, P = 0.255). Upon dividing IgLV3-21 group into subset #2, non-subset #2/IgHV M and IgHV UM, we did not find a significant difference regarding both OS (P = 0.714) and TTFT (P = 0.259).
Conclusion
Our results in line with previous publications suggest that the IgLV3-21 light chain expression identifies unfavourable CLL subgroup independent of the IgHV mutational status and is associated with presence of SF3B1 mutations. Subsequent studies in a larger CLL cohort will clarify the significance of IgLV3-21 for risk stratification of patients.
Keyword(s): Chronic lymphocytic leukemia