How I investigate Clonal cytogenetic abnormalities of undetermined significance

Abstract

Myelodysplastic syndromes are a group of hematopoietic stem cell diseases characterized by cytopenia(s), morphological dysplasia, and clonal hematopoiesis. In some patients, the cause of cytopenia(s) is uncertain, even after thorough clinical and laboratory evaluation. Evidence of clonal hematopoiesis has been used to support a diagnosis of myelodysplastic syndrome in this setting. In patients with cytopenia(s), the presence of clonal cytogenetic abnormalities, except for +8, del(20q) and -Y, can serve as presumptive evidence of myelodysplastic syndrome. Recent advances in next-generation sequencing have detected myeloid neoplasm-related mutations in patients who do not meet the diagnostic criteria for myelodysplastic syndrome. Various terms have been adopted to describe these cases, including clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). Similarly, studies have shown that certain chromosomal abnormalities, including ones commonly detected in myelodysplastic syndrome, may not be associated necessarily with an underlying myelodysplastic syndrome. These clonal cytogenetic abnormalities of undetermined significance (CCAUS) are similar to CHIP and CCUS. Here, we review the features of CCAUS, distinguishing CCAUS from clonal cytogenetic abnormalities associated with myelodysplastic syndrome, and the potential impact of CCAUS on patient management.

Hidden myelodysplastic syndrome (MDS): A prospective study to confirm or exclude MDS in patients with anemia of uncertain etiology

“…These diagnoses are challenging and also require additional hit(s) to complete a neoplastic hematopoiesis. 37 We found that TP53 and ZRSR2 mutations were associated with poor survival. All patients with these mutations died 20 months after diagnosis, although patient numbers were very small.…”

“…In this context, recent advances in NGS have detected myeloid neoplasm‐related mutations in patients who do not meet the diagnostic criteria for MDS and various terms have been adopted to describe these cases, including clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). These diagnoses are challenging and also require additional hit(s) to complete a neoplastic hematopoiesis …”

Clonal dominance of a donor‐derived del(20q) clone after allogeneic hematopoietic stem cell transplantation in an acute myeloid leukemia patient with del(20q)

“…Should del(20q) in our patient considered as the newly emerged isolated del(20q) in patients following cytotoxic therapies? The patients who acquired isolated del(20q) after cytotoxic therapy had innocuous BM finding in more than 77% of patients . Moreover, would the abnormal clone react equivalently in our patient as in the donor?…”

“…The patients who acquired isolated del(20q) after cytotoxic therapy had innocuous BM finding in more than 77% of patients. 11,12 Moreover, would the abnormal clone react equivalently in our patient as in the donor? The interplay of BM microenvironment and leukemia cells has been suggested, 13 and there is a chance that the del(20q) clone will progress to myeloid neoplasm in the BM microenvironment of someone previously diagnosed with AML harboring the same cytogenetic abnormality.…”

Pattern of chromosomal aberrations persisting over 30 years in a Chernobyl Nuclear Power Plant accident survivor: study using mFISH

“…Clonal aberrations can be frequently observed in irradiated patients and healthy controls [ 15 , 24 , 29 , 30 ], as well as in aged persons [ 31 ] and hypothetically reflect a stem cell pool depletion or an outgrowth of a particular lymphocyte population due to a premalignant process in a hematopoietic stem/progenitor cell or an immunological stimulation of a lymphocyte subpopulation. The time of persistence and dynamics of circulating clones are yet to be determined.…”