Pilot evaluation of optical genome mapping in chronic lymphocytic leukemia: complementing FISH analysis
Erdem S, Bayrak Tokaç AG, Aday A, et al. BMC Cancer. 2025;25(1):1687.
Summary. Researchers compared fluorescence in situ hybridization (FISH) and optical genome mapping (OGM) findings in 20 newly diagnosed or treatment-naïve patients with chronic lymphocytic leukemia (CLL). FISH detected no abnormalities in five patients; in three of these five patients, however, OGM identified alterations outside of the FISH-targeted regions. OGM detected no abnormalities in two patients. A total of 22 structural variants, including 12 intrachromosomal fusions, eight translocations, and two insertions; 32 copy number variants (CNVs), including 26 deletions and six duplications; and eight aneuploidies were identified among 18 patients with OGM. The authors concluded that OGM could be a utilized as a complementary tool to FISH in the cytogenetic assessment of CLL.
* PMID: 41184797, PMCID: PMC12581556
Clonal burden, immunoglobulin heavy chain variable gene somatic hypermutations, and immunoglobulin gene repertoire in Korean patients with chronic lymphocytic leukemia assessed by next-generation sequencing
Lee T, Chu D, Kim M, et al. Ann Lab Med. 2025. Epub ahead of print.
Summary. Analyzing data from 40 patients with CLL, researchers found that all patients had clonal immunoglobulin heavy chain (IGH) rearrangements and 92.5 percent had clonal immunoglobulin kappa (IGK) rearrangements. NGS-based IGH rearrangement showed a lower clonal size than flow cytometric immunophenotyping, especially when using the IGH leader primer. Immunoglobulin heavy chain variable (IGHV) somatic hypermutations (SHMs) were identified in 28 patients (70%) using the IGH leader primer and 26 patients (65.0%) using the IGH FR1 primer, with discrepancies between primer sets observed in four patients. Patients with genetic features linked to poor prognosis had a lower proportion of IGHV SMHs. The most common IGHV group was IGHV3 (58.3%) followed by IGHV4 (22.9%). Of 21 identified IGHVs, the most frequent were IGHV4-34 (14.6%) and IGHV3-23 (12.5%). IGHJ4 (56.3%) was the most commonly identified gene in the IGHJ repertoire, followed by IGHJ6 (18.8%).
* PMID: 41024698
Attenuated SARS-CoV-2-specific T-cell responses are associated with T follicular helper cell expansion in treatment-naïve patients with chronic lymphocytic leukemia
Šlisere B, Kārkliņš R, Rivkina A, et al. Pathogens. 2025;14(9):890.
Summary. Evaluating data from 38 treatment-naïve patients with CLL and 13 controls who received SARS-CoV-2 vaccination, researchers found that SARS-CoV-2 spike–specific immunoglobulin G (IgG) and IgA levels were similar between groups. Most patients mounted SARS-CoV-2-specific antibody responses to IgG (94.7%) and IgA (89.5%). Positive T cell response was detected in 30 patients (78.9%), and magnitude of response did not differ among patients with and without natural exposure to SARS-CoV-2. Patients with CLL had significantly increased frequency and absolute number of CD4+ T follicular helper (Tfh) and T follicular regulatory (Tfr) cells, compared to controls. Patients who lacked a virus-specific T-cell response exhibited significantly increased frequency and absolute number of Tfh cells, compared to patient responders and controls (all of whom had detectable virus-specific T-cell response).
* PMID: 41011790, PMCID: PMC12472264
Complex genetic landscape in CLL: clinical impact on patients’ survival and insights into the altered molecular pathways
Caputo C, Donadelli M, Scupoli M, et al. Mol Ther Oncol. 2025;33(4):201048.
Summary. Researchers analyzed real-world data to characterize the impact of molecular pathways on survival in CLL. Samples from 137 patients with newly diagnosed CLL were analyzed, and 96.3 percent exhibited TP53 single nucleotide polymorphisms (SNPs), most commonly Pro72Arg missense mutation (96.3%). Among those with p.Pro72Arg TP53 mutation, untreated patients showed longer median overall survival compared to treated patients; this mutation has been reported in healthy controls and thus is likely not involved in CLL development. Patients with Binet stage A had significantly improved survival over patients with Binet stage B/C, and patients with Binet stage B showed significantly greater survival compared to those with Binet stage C.
* PMID: 41035777, PMCID: PMC12481919
Germinal center trajectories and transcriptional signatures define CLL subtypes and their pathway regulators
Mohamed A, Giudice L, Basílio J, et al. PLoS One. 2025;20(10):e0335069.
Summary. Researchers analyzed bulk ribonucleic acid (RNA) data from patients with CLL and healthy donors to determine the transcriptional and mechanistic functions of CLL with (M-CLL) and without (U-CLL) IGHV mutations. CD27bright memory B cells (MBCs) clustered with M-CLL, indicating that M-CLL is more transcriptionally similar to CD27bright MBCs than U-CLL. There were 391 highly differentially expressed genes (DEGs) between M-CLL and CD27bright MBCs, and 471 between U-CLL and CD27bright MBCs. LPL, ZNF667, and ZNF667-AS1 could potentially stratify CLL based on IGHV mutation status. Further analysis showed that U-CLL had a similar dominant expression profile to dark zone and early intermediary stage from the germinal center, and M-CLL demonstrated similarity to a later intermediary stage, suggesting that both M- and U-CLL partially derived from germinal center reaction.
* PMID: 41124223, PMCID: PMC12543202
MYC target gene activation in chronic lymphocytic leukemia and Richter transformation: links to aggressiveness and tumor microenvironment interactions
Tsagiopoulou M, Rashmi S, Chatziaslani M, Gut I. Front Pharmacol. 2025;16:1642458
Summary. Analyzing CLL samples, including pre- and post-Richter transformation (RT) samples, researchers found that MYC target gene activation significantly increased in U-CLL versus M-CLL. Additionally, presence of trisomy 12 was linked to increased MYC activation, regardless of IGHV mutational status. MYC target genes were significantly elevated in RT compared to pre-RT. In CLL, MYC activation was associated with 45 of 51 pathways, whereas it was associated with 19 pathways in RT. In RT, MYC activation was correlated with cell cycling but was independent from B-cell receptor signaling. High MYC target gene activation was associated with significantly shorter time to first treatment, as well as increased tumor microenvironment interactions in both CLL and RT, particularly with myeloid cells.
* PMID: 40894230, PMCID: PMC12394460