| CMML |
|
| -WHO [1]: presence of mutations in genes often associated with CMML (TET2, SRSF2, ASXL1, SETBP1) in the proper clinical contest can be used to support diagnosis |
| -Associated with the following gene mutation combinations: TET2-SRSF2, biallelic TET2, SRSF2-RUNX1 [2,4,30]
| [ 2][4][30]
|
| Cytogenetics |
| -Three cytogenetic stratification systems have been proposed [23,24,25]
| [ 23][24][25]
| -Recurrent findings: |
| • Low risk karyotypes: normal karyotype, isolated loss of Y |
| • High risk karyotypes: chr7 abnormalities, complex karyotype, monosomal karyotype |
| Gene mutations: |
| -Unfavorable outcome: mutations in ASXL1 , RUNX1, NRAS and SETBP1 [2,30,31]
| [ 2 ] [ 30 ] [31]
| -Favorable outcome: TET2 mutations, especially in the absence of ASXL1 mutations ( TET2 MUT /ASXL1WT). These patients also show better response to HMA [32,33,34][32][33][34]. |
| Prognostic stratification: |
| -GFM Model | [ 2 ] | , stratification in 3 risk groups based on: Age > 65 years; Hb < 10 g/dL in females and <11 g/dL in males; WBC > 15 × 10 9 /L; Platelet count < 100 × 10 9 /L; ASXL1 mutations |
| -Mayo Molecular Model (MMM) | [ 31 ] | , stratification in 4 risk groups based on: Hb < 10 g/dL; AMC > 10 × 10 9 /L; Platelet count < 100 × 10 9 /L; Presence of circulating IMCs; ASXL1 mutations |
| -CPSS-Mol | [ 30 ] | , stratification in 4 risk groups based on: WBC ≥ 13 × 10 9 ; BM blasts ≥ 5%; RBC transfusion dependency; Genetic risk group (includes CMML-specific cytogenetic risk stratification | [ 23 ] | and mutations in ASXL1, RUNX1, NRAS and SETBP1 ). |
|
| aCML |
|
| -Associated with the following gene mutation combinations: ASXL1/SETBP1, SETBP1/SRSF2, ASXL1/EZH2, RUNX1/EZH2 [3,4,35]
| [3][4][35]
|
| Unfavorable outcome: mutations in TET2, RUNX1, NRAS and CUX1 [3,
| [4]3][4]
| Prognostic stratification: |
| Mayo Prognostic Model for aCML | [ 3 ], stratification in 2 risk groups based on: Age > 67 years; Hb < 10 g/dL; TET2 mutations
|
| MDS/MPN-RS-T |
|
| -WHO [1]: presence of a SF3B1 mutation. |
| -Associated with the following gene mutation combinations: SF3B1, either alone or in combination with DNMT3A or JAK2, or DNMT3A/JAK2 [4,26,36]
| [ 4][26][36]
|
| Unfavorable outcome: |
| -Presence of altered karyotype [4,26]
| [ 4][26]
| -Mutations in ASXL1, SETBP1, EZH2 [4,26]
| [ 4 ][26]
| Prognostic stratification: |
| Mayo Prognostic Model for MDS/MPN-RS-T | [ 26 ] | , stratification in 3 risk groups based on: Hb < 10 g/dL; Abnormal karyotype; mutations in ASXL1 or SETBP1 |
|
| MDS/MPN-U |
|
| - |
|
| Unfavorable outcome: |
| -Presence of chr7 abnormalities and complex karyotypes | [ 19]
| -Mutations in ASXL1, CBL, CEBPA, EZH2, STAG2, TP53 [4,27,37]
| [ 4 ][27][37]
| Prognostic stratification: |
| -Genomics-based stratification system (Figure 4), classification in 5 subtypes with prognostic relevance based on mutational profile | [ 4 ]
|
| JMML |
|
| -WHO [1]: presence of (1 finding sufficient): |
| • Somatic mutation: PTPN11, KRAS, NRAS |
| • Clinical diagnosis of NF1 or NF1 mutation |
| • Germline CBL mutation CBL LOH |
|
| Prognostic stratification: |
| According to the methylation level, three groups that correlate molecular features and clinical outcome have been proposed | [ 38]:
| • High: characterized by somatic PTPN11 mutations and poor clinical outcome |
| • Intermediate: enriched in somatic KRAS mutations and monosomy 7 |
| • Low: characterized by somatic NRAS and CBL mutations and a favorable prognosis |
|