2016 WHO diagnostic criteria for MDS/MPN overlap neoplasms
| MPN/MDS overlap subtypes . | 2016, WHO diagnostic criteria* . | Frequency of somatic gene mutations . | Median age at Dx, y . | Median OS . | Rate of LT . |
|---|---|---|---|---|---|
| aCML | WBC count > 13 × l09/L with increased and dysplastic neutrophils. No or minimal absolute basophils and monocytosis. Hypercellular BM with granulocytic proliferation and dysplasia (neutrophil precursors greater than equal to 10%). | ASXL1 (60%), SETBP1 (48%), N/KRAS (35%), TET2 (30%), EZH2 (13%) and <10% for the following: CSF3R, ETNK1, CBL, FLT3, RUNX1, CEBPA, IDH1/2 | >60 | 22 mo | 30-40% |
| CMML | Persistent PB monocytosis ≥ 1 × 109/L. Dysplasia in ≥1 lineage, if no dysplasia, then must include an acquired clonal cytogenetic or molecular genetic abnormality (TET2, ASXL1, SRSF2, and/or SETBP1). | TET2 (60%), SRSF2 (50%), ASXL1 (40%), NRAS (15%), CBL (15%), RUNX1 (15%), SETBP1 (15%), KRAS (10%), IDH1/2 (5-10%), and <10% for the following: JAK2, SF3B1, U2AF1, EZH2, DNMT3A, PTPN11, ZRSR2, FLT3 | 71-74 | 28-32 mo | 15-30% |
| MDS/MPN-RS-T | Platelet count ≥ 450 × 109/L. 15% ring sideroblasts in the BM or >5% with SF3B1 mutation. Presence of megakaryocytic atypia resembling ET or MF. | SF3B1 (93%), JAK2 (57%), TET2 (25%), DNMT3A (15%), ASXL1 (15%), and <10% for the following: SRSF2, CBL, SETBP1, IDHl/2 | 71-75 | 76 mo | 1-2% |
| MDS/MPN-U | Myeloid neoplasm with mixed MDS and MPN features, not meeting WHO criteria for other MDS/MPN overlap neoplasms, MDS or MPN. | TET2 (30%), RUNX1 (14%), CBL (11%), EZH2 (10%), N/KRAS (10%), SETBP1 (10%), and <10% for the following: DNMT3A, CEBPA, IDH1/2 | 70 | 12-28 mo | Unknown |
| JMML | PB monocyte count ≥ 1 × 109/L. Splenomegaly. Genetic features (must include 1 of the following): somatic mutation in PTPN11,† KRAS,† or NRAS†; diagnosis of neurofibroatosis-1 or NF1 mutation; or germline CBL mutation and loss of heterozygosity of CBL. If no genetic features then, must have a clonal chromosomal abnormality or all of the following: GM-CSF hypersensitivity, hyperphosphorylation of STAT5, fetal hemoglobin increased for age, myeloid or erythroid precursors on PB smear | PTPN11† (38%), NRAS† (18%), KRAS† (14%), CBL (12-18%), NF1 (5-10%) | 1.4-2 | 10-12 mo | Infrequent |
| MPN/MDS overlap subtypes . | 2016, WHO diagnostic criteria* . | Frequency of somatic gene mutations . | Median age at Dx, y . | Median OS . | Rate of LT . |
|---|---|---|---|---|---|
| aCML | WBC count > 13 × l09/L with increased and dysplastic neutrophils. No or minimal absolute basophils and monocytosis. Hypercellular BM with granulocytic proliferation and dysplasia (neutrophil precursors greater than equal to 10%). | ASXL1 (60%), SETBP1 (48%), N/KRAS (35%), TET2 (30%), EZH2 (13%) and <10% for the following: CSF3R, ETNK1, CBL, FLT3, RUNX1, CEBPA, IDH1/2 | >60 | 22 mo | 30-40% |
| CMML | Persistent PB monocytosis ≥ 1 × 109/L. Dysplasia in ≥1 lineage, if no dysplasia, then must include an acquired clonal cytogenetic or molecular genetic abnormality (TET2, ASXL1, SRSF2, and/or SETBP1). | TET2 (60%), SRSF2 (50%), ASXL1 (40%), NRAS (15%), CBL (15%), RUNX1 (15%), SETBP1 (15%), KRAS (10%), IDH1/2 (5-10%), and <10% for the following: JAK2, SF3B1, U2AF1, EZH2, DNMT3A, PTPN11, ZRSR2, FLT3 | 71-74 | 28-32 mo | 15-30% |
| MDS/MPN-RS-T | Platelet count ≥ 450 × 109/L. 15% ring sideroblasts in the BM or >5% with SF3B1 mutation. Presence of megakaryocytic atypia resembling ET or MF. | SF3B1 (93%), JAK2 (57%), TET2 (25%), DNMT3A (15%), ASXL1 (15%), and <10% for the following: SRSF2, CBL, SETBP1, IDHl/2 | 71-75 | 76 mo | 1-2% |
| MDS/MPN-U | Myeloid neoplasm with mixed MDS and MPN features, not meeting WHO criteria for other MDS/MPN overlap neoplasms, MDS or MPN. | TET2 (30%), RUNX1 (14%), CBL (11%), EZH2 (10%), N/KRAS (10%), SETBP1 (10%), and <10% for the following: DNMT3A, CEBPA, IDH1/2 | 70 | 12-28 mo | Unknown |
| JMML | PB monocyte count ≥ 1 × 109/L. Splenomegaly. Genetic features (must include 1 of the following): somatic mutation in PTPN11,† KRAS,† or NRAS†; diagnosis of neurofibroatosis-1 or NF1 mutation; or germline CBL mutation and loss of heterozygosity of CBL. If no genetic features then, must have a clonal chromosomal abnormality or all of the following: GM-CSF hypersensitivity, hyperphosphorylation of STAT5, fetal hemoglobin increased for age, myeloid or erythroid precursors on PB smear | PTPN11† (38%), NRAS† (18%), KRAS† (14%), CBL (12-18%), NF1 (5-10%) | 1.4-2 | 10-12 mo | Infrequent |
Dx, diagnosis; ET, essential thrombocythemia; GM-CSF, granulocyte-macrophage colony-stimulating factor; LT, Leukemic transformation; MF, myelofibrosis; OS, overall survival; STAT5- signal tansducer and activator of transcription 5.
All MDS/MPN overlap subtypes are negative for BCR-ABL1 fusions, or rearrangements involving PDGFRA, PDGFRB, FGFR1 and PCM1-JAK2 and have <20% blasts in the PB and BM.1
†Germline mutations (indicative of Noonan syndrome) need to be excluded.