Table 1 Current clinical classifications of myeloid malignancies and their associated driver mutations, secondary mutations, and physiology [3, 5, 16, 18, 21, 41, 83,84,85,86,87]

MPN

ET^5,83–85

JAK2V617F, CALR, MPL

ASXL1, SRSF2, IDH2/EZH2, SETBP1, TET2

Thrombocytosis; proliferation of mature megakaryocytes in BM

PV ^5,83–85

JAK2, JAK2V617F

ASXL1, SRSF2, IDH2/EZH2, SETBP1, TET2

Elevated hemoglobin, hematocrit, or red blood cell mass; panmyelosis; no megakaryocytic atypia

PMF ^5,83–85

JAK2, CALR, MPL

ASXL1, SRSF2, IDH2/EZH2, SETBP1, TET2

Megakaryocytic proliferation and atypia in BM; fibrosis in BM; anemia, leukocytosis, high LDH

CNL ^5,83–85

CSF3R

SETBP1, ASXL1, SRSF2

Persistent neutrophilia; granulocytes at segmented stage in PB

CML^{5,21,41,83–85}

BCR/ABL1

*Rare - ABL1

Proliferation of mature myeloid cells; Philadelphia chromosome t(9;22) translocation.

MDS

SF3B1, del(7q)^3,5,16,83,85

SF3B1, del(7q)

TET2, SRSF2, ASXL1, DNMT3A, RUNX1, U2AF1, EZH2

Morphologic dysplasia; <5% BM blasts; <2% PB blasts; ≥1 cytopenia; no cytoses

del(5q) ^3,5,16,83,85

del(5q)

TET2, SRSF2, ASXL1, DNMT3A, RUNX1, U2AF1, EZH2

Morphologic dysplasia; <5% BM blasts; <2% PB blasts; ≥1 cytopenia; possible thrombocytosis

EB^5,21,83,86

SF3B1, del(5q), del(7q)

TET2, SRSF2, ASXL1, DNMT3A, RUNX1, U2AF1, EZH2

Morphologic dysplasia; 5–9% BM blasts; 2–9% PB blasts; ≥1 cytopenia; no cytoses

TP53^3,5,83,85,86

Multi-hit TP53

Del(17p)

Morphologic dysplasia; 0–9% BM and PB blasts; ≥1 cytopenia

MDS/AML^5,21,86

SF3B1, del(5q), del(7q)

TET2, SRSF2, ASXL1, DNMT3A, RUNX1, U2AF1, EZH2

10–19% BM or PB blasts

AML

Gene or Chromosome^{3,5,18,41,83,85–87}

NPM1, DNMT3A, FLT3

NRAS, KRAS, KIT, SF3B1, ZRSR2, U2AF1, SRSF2, IDH1, IDH2, TET2, ASXL1, RUNX1, GATA2, CEBPA, BCOR, EZH2, WT1

Clonal expansion of myeloid precursors with ≥ 20% blasts in BM or PB; inhibition of normal hematopoiesis, causing cytopenias; variable differentiation in myeloid lineages

APL^{5,18,83,85–87}

PML/RARA

FLT3-ITD, FLT3-D835, NRAS, KRAS, DNMT3A, IDH1/2, TET2, ASXL1

Severe bleeding; coagulopathy due to DIC; promyelocytes dominate BM

TP53^{3,5,18,85–87}

Multi-hit TP53

-

Complex karyotypes; associated with poor prognosis and resistance to standard chemotherapy

Myelodysplasia-related^{3,5,18,21,83,86,87}

TP53, RUNX1, ASXL1, EZH2, STAG2

SF3B1, SRSF2, U2AF1, ZRSR2

Arises from MDS; characterized by dysplasia in ≥ 50% of cells in at least 2 lineages

t-AML^5,16,18,83

NPM1, DNMT3A, FLT3

-

Previously treated with leukemogenic therapies

Secondary AML^5,16,18,87

ASXL1, SRSF2,

SF3B1, U2AF1, ZRSR2,

EZH2, BCOR, STAG2

Arises from antecedent hematologic disorder

MDS/MPN

CMML^5,83,86

SRSF2, TET2, ASXL1

SETBP1, NRAS/KRAS, RUNX1, CBL, EZH2, NPM1

Monocytosis; cytopenia; presence of clonality; <20% blasts in PB and BM

RS ^5,83

SF3B1

TET2, SRSF2, U2AF1

Ring sideroblasts present in BM; dyserythropoiesis; anemia​

aCML^5,21,83

*BCR/ABL1⁻

SETBP1, ASXL1, EZH2, NRAS, KRAS

Persistent leukocytosis; <20% blasts in PB; dysgranulopoiesis; no BCR/ABL1 fusion