期刊
BRITISH JOURNAL OF HAEMATOLOGY
卷 198, 期 1, 页码 103-113出版社
WILEY
DOI: 10.1111/bjh.18129
关键词
CHIP and FCR; CLL; t-MN
类别
资金
- Lion's Cancer Research Foundation, Uppsala
- AIRC 5x1000 call Metastatic disease: the key unmet need in oncology [21267]
- Ministero della Salute, Rome, Italy [NET--2018--12365935]
- PRIN grant [2017WXR7ZT]
- Italian Ministry of Health, Rome, Italy [RF-2018-12 365 790]
- Operational Programme Competitiveness, Entrepreneurship and Innovation (NSRF 2014--2020)
- European Union [MIS 5002462]
This study confirms the potential impact of clonal hematopoiesis of indeterminate potential (CHIP) on the development of therapy-related myeloid neoplasms (t-MN) in patients with chronic lymphocytic leukemia (CLL). The findings suggest a significantly higher prevalence of CHIP in CLL patients who develop t-MN compared to the general CLL population.
Clonal haematopoiesis of indeterminate potential (CHIP) may predispose for the development of therapy-related myeloid neoplasms (t-MN). Using target next-generation sequencing (t-NGS) panels and digital droplet polymerase chain reactions (ddPCR), we studied the myeloid gene mutation profiles of patients with chronic lymphocytic leukaemia (CLL) who developed a t-MN after treatment with chemo-(immuno)therapy. Using NGS, we detected a total of 30 pathogenic/likely pathogenic (P/LP) variants in 10 of 13 patients with a t-MN (77%, median number of variants for patient: 2, range 0-6). The prevalence of CHIP was then backtracked in paired samples taken at CLL diagnosis in eight of these patients. Six of them carried at least one CHIP-variant at the time of t-MN (median: 2, range: 1-5), and the same variants were present in the CLL sample in five cases. CHIP variants were present in 34 of 285 patients from a population-based CLL cohort, which translates into a significantly higher prevalence of CHIP in patients with a CLL who developed a t-MN, compared to the population-based cohort (5/8, 62.5% vs. 34/285, 12%, p = 0.0001). Our data show that CHIP may be considered as a novel parameter affecting treatment algorithms in patients with CLL, and highlight the potential of using chemo-free therapies in CHIP-positive cases.
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