Telomere length is recognized as a significant and independent prognostic factor in multiple cancers. Shorter telomere lengths or more telomere erosion was found in Americans of African ancestry (AA) with CLL compared to those Americans with CLL of European ancestry (EA), even after accounting for other known prognostic factors.
Who Performed the Research and Where Was it Presented:
At ASH 2022, a consortium of researchers across the USA led by a group from MAYO presented the finding.
Telomeres are the repeated sequences of DNA found at the very end of a chromosome. Telomeres’ role is to protect the ends of chromosomes. Each time a cell divides, the telomeres become slightly shorter. Eventually, they become too short, so the cell can no longer divide successfully, leading to cell death. In CLL, telomere shortening can lead to a loss of function of DNA damage checkpoint genes. This, in turn, allows further cell proliferation and telomere shortening.
DNA was extracted from CLL cells and used to measure the average telomere length through quantitative PCR (qPCR). Five CLL samples with known telomere lengths were included in every analysis to account for variability.
- Telomere erosion was evaluated in 133 AA with a mean age of 62.7 years ±13.6) and 147 age-matched EA CLL patients (mean age at sample collection at 61.6 years ±10.2).
- The AA samples were collected from 95 (71%) male patients, and 71% presented with unmutated IGHV or u-IGHV.
- EA samples were collected from 110 (77%) male patients and 66% u-IGHV.
- As expected, we observed shorter telomere length in u-IGHV CLL (median 3.7 kb; range 0.8-44.9) compared to mutated immunoglobulin heavy-chain variable region (m-IGHV) CLL (median 6.8 kb; range 1.8-44.7; p<0.0001) in the total cohort.
- AA CLL presented shorter telomere lengths (median 4.2 kb; range 0.6-13.1) than EA CLL (median 4.7 kb; range 1.1-44.9; p=0.005; Figure 1A).
- We highlight that the differences in telomere length observed were restricted to the CD5+/CD19+ cells or CLL cells, with no difference observed in germline samples collected from AA and EA patients.
- When stratifying by IGHV mutation status, shorter telomere length was observed in u-IGHV when compared to m-IGHV among both AA CLL (median 3.5 kb and 6.3, respectively; p<0.0001) and EA CLL (median 3.9 kb and 7.5, respectively; p<0.0001).
- The significantly shorter telomere lengths in AA CLL remained significant (p=0.006) after accounting for IGHV status, age, sex, number of mutated CLL driver genes, and Rai stage in multivariate analyses.
These results demonstrated increased telomere erosion or shorter telomere length in AA CLL compared to EA CLL, even after accounting for other known prognostic factors. At the same ASH conference, another paper, Racial/Ethnic, Sex, and Income Disparities in Overall Survival (OS) in Chronic Lymphocytic Leukemia (CLL) Patients in the Era of Targeted Therapy: Surveillance, Epidemiology, and End Results (SEER) Registry Analysis (2009-2019) demonstrated poorer overall survival in Non-Hispanic-Black Americans. Could these findings contribute to those worse clinical outcomes? More research is needed.
CLL Society has partnered with the Mayo Clinic on this trial to explore what genetic factors are involved.
Links and Resources:
Watch my review of this abstract:
The ASH abstract is available at Chronic Lymphocytic Leukemia in African Ancestry Population Is Characterized By Increased Telomere Erosion.
Stay strong. We are all in this together.
Brian Koffman MDCM (retired) MS Ed (he, him, his)
Co-Founder, Executive VP, and Chief Medical Officer
CLL Society, Inc.