IDH2), cohesion complex (STAG2), transcriptional regulation (TP53, RUNX1, GATA2), chromatin modification (ASXL1, EZH2), and signal transduction (JAK2, KRAS, NRAS, CBL).46,47
Mutations in the Ten‐Eleven Translocation‐2 gene (TET2) were recently identified in MDS and other myeloid neoplasms.48‐50 TET2 mutations occur in 10–26% of MDS patients. The enzyme converts methylcytosine to hydroxymethylcytosine and thus may play a role in DNA methylation and may predict the response to hypomethylating agents.51
The spliceosome gene SF3B1 is a recurrent mutation in MDS and is associated with ring sideroblasts.52 SF3B1 mutation is an early event in MDS pathogenesis and predicts a favourable prognosis.53 TP53 mutations are detected in approximately 5–20% of cases in MDS54 and are associated with higher‐risk MDS, therapy‐related MDS, and MDS with complex cytogenetics.
Diagnostic criteria
The National Comprehensive Cancer Network recommended the following diagnostic criteria proposed by the International Working Group (IWG).55 Minimal diagnostic criteria for this disease include two prerequisites:
1 Stable cytopenia (for ≥6 months or ≥2 months if accompanied by a specific karyotype or bilineage dysplasia)
2 The exclusion of other potential disorders as a primary reason for dysplasia or cytopenia
In addition, the diagnosis of MDS requires ≥1 of three MDS‐related criteria:
1 Dysplasia (≥10% in ≥1 of the 3 major bone marrow lineages)
2 A blast cell count of 5% to 19%
3 A specific MDS‐associated karyotype (e.g. del(5q), del(20q), +8, or ‐7/del(7q))
Classification
A number of morphological classifications are in place to classify patients with MDS. The current term, MDS, was adopted by the French, American, and British (FAB) Cooperative Group in 1976 in their classification scheme of these disorders. The WHO classification was proposed as a modification of the FAB system56 and was revised in 201657 from the previous version (2008)58 (Table 26.2).
Table 26.2 Classification scheme of myelodysplastic syndromes (MDS) in the 2016 revision of the World Health Organization (WHO) classification, and corresponding terminology in the 2008 WHO classification.
Source: Adapted from Sanz‐De Pedro et al.46
| 2016 WHO classification | 2008 WHO classification |
|---|---|
| MDS with single‐lineage dysplasia | Refractory cytopenia with unilineage dysplasia |
| MDS with ring sideroblasts (MDS‐RS) MDS‐RS and single‐lineage dysplasia MDS‐RS and multilineage dysplasia | Refractory anaemia with ring sideroblasts |
| MDS with multilineage dysplasia | Refractory cytopenia with multilineage dysplasia |
| MDS with excess blasts‐1 | Refractory anaemia with excess blasts‐1 |
| MDS with excess blasts‐2 | Refractory anaemia with excess blasts‐2 |
| MDS, unclassifiable (MDS‐U) MDS‐U with 1% blood blasts MDS‐U with single‐lineage dysplasia and pancytopenia MDS‐U based on defining cytogenetic abnormality | MDS, unclassifiable (MDS‐U) |
| RCC (refractory cytopenia of childhood (provisional) | Childhood myelodysplastic syndrome (provisional) |
The 2016 WHO classification identifies six entities of MDS: MDS with single‐lineage dysplasia (MDS‐SLD), MDS with ring sideroblasts (MDS‐RS), MDS with multilineage dysplasia (MSD‐MLD), MDS with excess blasts (MDS‐EB), MDS with isolated del(5q), and MDS unclassifiable (MDS‐U). There is an additional provisional entity, ‘refractory cytopenia of childhood’ (RCC) (Table 26.3).
Table 26.3 WHO 2016 classification.
Source: Adapted from Hong et al.44
| Type | Dysplastic lineages | Cytopeniaa | Ring sideroblasts in erythroid elements of BM | Blasts | Cytogenetics |
|---|---|---|---|---|---|
| MDS‐SLD | 1 | 1 or 2 | RS <15% (or <5%b) | PB <1% BM <5% No Auer rods | Any, unless fulfils criteria for isolated del(5q) |
| MDS‐MLD | 2 or 3 | 1–3 | RS <15% (or <5%b) | PB <1% BM <5% No Auer rods | Any, unless fulfils criteria for isolated del(5q) |
| MDS‐RS‐SLD: | 1 | 1 or 2 | RS ≱15% (or ≱5%b) | PB <1% BM <5% No Auer rods | Any, unless fulfils criteria for isolated del(5q |
| MDS‐RS‐MLD | 2 or 3 | 1–3 | RS ≱15% (or ≱5%b) | PB <1% BM <5% No Auer rods | Any, unless fulfils criteria for isolated del(5q |
| MDS with isolated del(5q) | 1–3 | 1–2 | None or any | PB <1% BM <5% No Auer rods | del(5q) alone or with one additional abnormality except ‐7 or del(7q) |
| MDS‐EB‐1 | 0–3 | 1–3 | None or any | PB 2~4% or BM 5~9%, No Auer rods | Any |
| MDS‐EB‐2 | 0–3 | 1–3 | None or any | PB 5~19% or BM 10%~19% or Auer | Any |
| MDS‐U with 1% peripheral blood blast | 1–3 | 1‐3 | None or any | PB=1%c BM<5% Auer rods | Any |
| MDS‐U with single‐lineage dysplasia and pancytopenia | 1 |
|