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Clonal hematopoiesis of indeterminate potential
- Clonal hematopoiesis refers to a population of blood and/or bone marrow cells that share an acquired mutation.
- Unmutated gene is called “wild type” allele.
- CHIP is a condition in which there are clonal mutations of myeloid malignancy associated genes but do not yet meet diagnostic criteria for diagnosis of any hematologic neoplasm and do not have a clinically significant cytopenia.
- Clonal mutations are detected when whole genome sequencing peripheral blood sample is done using NGS technique.
- Genes in which mutations are commonly seen include: DNMT3A, TET2 and ASXL1.
- This is a type of age related somatic mosaicism
- Usually seen after 65 years of age
- Seen in 10-40% of people above age of 65 years.
- Other risk factors: smoking, male sex, exposure to cytotoxic therapies, and aplastic anaemia
- Differentiating true CHIP from sequencing artifacts and germline variants is a considerable bioinformatic challenge.
- A cutoff of ≥ 2% variant allele fraction (VAF) is necessary criterion for CHIP (VAF is percentage of mutated DNA sequence reads at a given genetic locus) If VAF is >25% and if there is strong family history of cancer, germline mutations must be exluded by testing dermal fibroblasts.
- It is considered as a premalignant condition, but routine testing for CHIP is not recommended.
- It is linked to cardiovascular diseases, autoimmune diseases and other non-hematological diseases.
- Management: No treatment is necessary. Monitoring once in 3-6 months with history, examination and CBC.
- Related entities:
- Age-Related Clonal Haematopoiesis (ARCH): It is clonal hematopoiesis associated with aging.
- Clonal cytopenia of undetermined significance (CCUS): It is a condition in which there is clonal mutation and one or more clinically meaningful unexplained cytopenia, but it does not meet WHO defined criteria for a hematological neoplasm.
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