CHIP/CCUS

Clonale hematopoiese

Clonal haematopoiesis (CH) refers broadly to the presence of a population of cells derived from a mutated multipotent stem/progenitor cell harbouring a selective growth advantage in the absence of unexplained cytopenias, haematological cancers, or other clonal disorders. The incidence of CH increases with age.

Clonal haematopoiesis of indeterminate potential (CHIP) is defined in the classification as a term referring specifically to CH harbouring somatic mutations of myeloid malignancy-associated genes detected in the blood or bone marrow at a variant allele fraction (VAF) of ≥ 2% (≥4% for X-linked gene mutations in males) in individuals without a diagnosed haematologic disorder or unexplained cytopenia. The significance of variants detected at lower levels is unclear at present.

Clonal cytopenia of undetermined significance (CCUS) is defined as CHIP detected in the presence of one or more persistent cytopenias that are otherwise unexplained by haematologic or non-haematologic conditions and that do not meet diagnostic criteria for defined myeloid neoplasms.

Cytopenia definitions are harmonized for CCUS, MDS, and MDS/MPN; they include

• Hb <13 g/dL(<7.8 mmol/L) in males and <12 g/dL (<7.2 mmol/l) in females for anaemia;

• absolute neutrophil count <1.8 10E9/L for leukopenia;

• platelets <150 10E9/L for thrombocytopenia.

Twee entiteiten die niet als MDS kunnen worden geclassificeerd:

• CCUS: clonal cytopenias of undetermined significance)

  • Aanhoudende cytopenie zonder dysplasie en zonder (specifieke) cytogenetische afwijkingen

  • Risico op hematologische maligniteit is onbekend

• CHIP: clonal haematopoiesis of indeterminate potential

  • Klonale MDS-geassocieerde genafwijking zonder dysplasie in het beenmerg en zonder cytopenie

    • o.a. voorkomend bij DNMT3A, TET2 en ASXL1 mutaties

    • Verhoogd risico op hematologische maligniteit (mn bij grote kloon)