The Progression to Myelodysplastic Syndromes (MDS)

There are several pre-MDS disorders that share some characteristics of MDS (clonality, dysplasia, cytopenia), but do not meet the criteria for MDS diagnosis (missing one or more of these characteristics).1-3

These pre-MDS conditions may develop into MDS or other hematopoietic neoplasms over time.1 Initial genetic events (eg, somatic mutations) responsible for MDS promote the acquisition of secondary genetic changes, which typically results in chromosomal changes that have been associated with progression to acute myeloid leukemia (AML).4

Genetic evolution and progression to MDS and AML2-5

AML, acute myeloid leukemia; ARCH, age-related clonal hematopoiesis; CCUS, clonal cytopenia of unknown significance; CHIP, clonal hematopoiesis of indeterminate potential; ICUS, idiopathic cytopenia of undetermined significance; MDS, myelodysplastic syndromes; RBC, red blood cell; WBC, white blood cell.

Pre-MDS disorders and risk for progression to MDS2

Pre-MDS Disorder Description Risk of Progression
ICUS, idiopathic cytopenia of undetermined significance
  • One or more cytopenias with no known etiology, but do not meet the criteria for MDS (eg, no evidence of substantial dysplasia)1,6
  • Can occur with or without clonal hematopoiesis1,6
Very low2
CHIP/ARCH, clonal hematopoiesis of indeterminate potential/age-related clonal hematopoiesis
  • Evidence of clonal hematopoiesis as defined by somatic mutations in MDS-related genes, but no evidence of dysplasia or cytopenias1,6
  • Some patients with ICUS may have CHIP, differing only from lower-risk MDS by their lack of dysplasia, and currently, an undetermined disease risk.2 Some individuals with ICUS will subsequently be diagnosed with MDS or AML2
Very low2,6
CCUS, clonal cytopenia of unknown significance
  • One or more cytopenias with no known etiology that do not meet the criteria for MDS (eg, no evidence of substantial dysplasia), but have somatic mutations in MDS-related genes1,6

References: 1. Valent P, Orazi A, Steensma DP, et al. Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions. Oncotarget. 2017;8(43):73483-73500. 2. Steensma DP, Bejar R, Jaiswal S, et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood. 2015;126(1):9-16. 3. Santini V. Society of Hematologic Oncology (SOHO) state of the art updates and next questions: myelodysplastic syndromes. Clin Lymphoma Myeloma Leuk. 2018;18(8):495-500. 4. Sperling AS, Gibson CJ, Ebert BL. The genetics of myelodysplastic syndrome: from clonal hematopoiesis to secondary leukemia. Nat Rev Cancer. 2017;17(1):5-19. 5. Steensma DP. Myelodysplastic syndromes: diagnosis and treatment. Mayo Clin Proc. 2015;90(7):969-983. 6. Bejar R. CHIP, ICUS, CCUS and other four-letter words. Leukemia. 2017;31(9):1869-1871.