Somatic mutations that characterize the different types of MDS/MPN
| Myeloid neoplasm according to the 2008 WHO classification . | Main diagnostic/clinical feature(s) . | Most common mutant gene(s) . |
|---|---|---|
| CMML (classified as MDS/MPN) | Persistent peripheral blood monocytosis (>1 × 109/L). | Co-occurrence of TET2 and SRSF2 mutations, or combinations of ASXL1 mutations with other mutant driver genes. ASXL1 mutation is associated with poor overall survival and high risk of progression to AML |
| aCML (classified as MDS/MPN) | Peripheral leukocytosis (≥13 × 109/L) with dysgranulopoiesis and 10% or more circulating immature granulocytes. | Combinations of founding mutations in various genes and subclonal mutations of SETBP1 or ASXL1. |
| CNL (classified as MPN) | Neutrophilic leukocytosis (≥25 × 109/L) with less than 10% circulating immature granulocytes. | Activating somatic mutations of CSF3R (encoding the receptor for G-CSF) in the vast majority of patients. Oncogenic lesions can be classified as truncation or membrane proximal mutations, involving different preferential downstream kinase signaling. |
| JMML (classified as MDS/MPN) | Persistent peripheral blood monocytosis (>1 × 109/L) in children. | Somatic mutations of the RAS pathway (NRAS, KRAS, NF1, PTPN11, and CBL). Heterozygous germ-line CBL mutations may predispose to JMML. Subclonal driver mutations of SETBP1 and JAK3 may cause disease progression. |
| RARS-T (classified as a provisional entity within MDS/MPN) | Macrocytic anemia, ring sideroblasts, and thrombocytosis. | Combinations of a founding somatic mutation of SF3B1 and subclonal driver mutations of JAK2 or MPL (and likely of other as-yet-unknown genes). |
| Myeloid neoplasm according to the 2008 WHO classification . | Main diagnostic/clinical feature(s) . | Most common mutant gene(s) . |
|---|---|---|
| CMML (classified as MDS/MPN) | Persistent peripheral blood monocytosis (>1 × 109/L). | Co-occurrence of TET2 and SRSF2 mutations, or combinations of ASXL1 mutations with other mutant driver genes. ASXL1 mutation is associated with poor overall survival and high risk of progression to AML |
| aCML (classified as MDS/MPN) | Peripheral leukocytosis (≥13 × 109/L) with dysgranulopoiesis and 10% or more circulating immature granulocytes. | Combinations of founding mutations in various genes and subclonal mutations of SETBP1 or ASXL1. |
| CNL (classified as MPN) | Neutrophilic leukocytosis (≥25 × 109/L) with less than 10% circulating immature granulocytes. | Activating somatic mutations of CSF3R (encoding the receptor for G-CSF) in the vast majority of patients. Oncogenic lesions can be classified as truncation or membrane proximal mutations, involving different preferential downstream kinase signaling. |
| JMML (classified as MDS/MPN) | Persistent peripheral blood monocytosis (>1 × 109/L) in children. | Somatic mutations of the RAS pathway (NRAS, KRAS, NF1, PTPN11, and CBL). Heterozygous germ-line CBL mutations may predispose to JMML. Subclonal driver mutations of SETBP1 and JAK3 may cause disease progression. |
| RARS-T (classified as a provisional entity within MDS/MPN) | Macrocytic anemia, ring sideroblasts, and thrombocytosis. | Combinations of a founding somatic mutation of SF3B1 and subclonal driver mutations of JAK2 or MPL (and likely of other as-yet-unknown genes). |
CNL has been included because of its overlapping features with aCML.