Identification of four autophagy-related genetic variants as risk factors for chronic lymphocytic leukemia.

We investigated the influence of 55,583 autophagy-related single nucleotide polymorphisms (SNPs) on chronic lymphocytic leukemia (CLL) risk across four independent populations comprising 5,472 CLL cases and 726,465 controls. We also examined their impact on overall survival (OS), time to first treatment (TTFT), autophagy flux, and immune responses. A meta-analysis of the four populations identified, for the first time, significant associations between CDKN2A (rs3731204) and BCL2 (rs4940571, rs12457371, rs1026825) SNPs and CLL risk, with CDKN2A showing the strongest association (p=1.

Chromoanagenesis Detection in Chronic Lymphocytic Leukemia.

Chromoanagenesis events have been identified in chronic lymphocytic leukemia (CLL), the most common leukemia in Western countries. Among the three events included within this term, chromothripsis is the most frequently reported. Its prevalence in CLL is low, ranging from 1 to 3% of patients in unselected cohorts, and it has been associated with poor prognostic factors, such as abnormal TP53 and genomic complexity, and dismal outcome.

Complex Karyotype Detection in Chronic Lymphocytic Leukemia: A Comparison of Parallel Cytogenetic Cultures Using TPA and IL2+DSP30 from a Single Center.

Current CLL guidelines recommend a two parallel cultures assessment using TPA and IL2+DSP30 mitogens for complex karyotype (CK) detection. Studies comparing both mitogens for CK identification in the same cohort are lacking. We analyzed the global performance, CK detection, and concordance in the complexity assessment of two cytogenetic cultures from 255 CLL patients.

Abnormalities Are Underlying the Poor Outcome Associated with Chromothripsis in Chronic Lymphocytic Leukemia Patients with Complex Karyotype.

Chromothripsis (cth) has been associated with a dismal outcome and poor prognosis factors in patients with chronic lymphocytic leukemia (CLL). Despite being correlated with high genome instability, previous studies have not assessed the role of cth in the context of genomic complexity. Herein, we analyzed a cohort of 33 CLL patients with cth and compared them against a cohort of 129 non-cth cases with complex karyotypes.

Optical Genome Mapping: A Promising New Tool to Assess Genomic Complexity in Chronic Lymphocytic Leukemia (CLL).

Novel treatments in chronic lymphocytic leukemia (CLL) have generated interest regarding the clinical impact of genomic complexity, currently assessed by chromosome banding analysis (CBA) and chromosomal microarray analysis (CMA). Optical genome mapping (OGM), a novel technique based on imaging of long DNA molecules labeled at specific sites, allows the identification of multiple cytogenetic abnormalities in a single test. We aimed to determine whether OGM is a suitable alternative to cytogenomic assessment in CLL, especially focused on genomic complexity.

Chromosome banding analysis and genomic microarrays are both useful but not equivalent methods for genomic complexity risk stratification in chronic lymphocytic leukemia patients.

Genome complexity has been associated with poor outcome in patients with chronic lymphocytic leukemia (CLL). Previous cooperative studies established five abnormalities as the cut-off that best predicts an adverse evolution by chromosome banding analysis (CBA) and genomic microarrays (GM). However, data comparing risk stratification by both methods are scarce.