Table 1.
Hematopoietic TF mutations and platelet defects
| TF | Chromosome location | Selected gene targets | Platelet dysfunction* | Associated hematologic abnormalities |
|---|---|---|---|---|
| RUNX1 | 21q22.3 | ALOX12, PF4, MYL9, PRKCQ, MPL, MYH9, MYH10, NFE2, PCTP, PLDN, ANKRD26 | Yes | Increased risk of MDS/AML |
| FLI1 | 11q24.1-24.3 | ITGA2B, GP1BA, GP6, GP9, MPL, PF4, NFE2, RAB27B, ANKRD26 | Yes | Unknown |
| GATA1 | Xp11.23 | GP1BA, GP1BB, ITGA2B, GP9, PF4, MPL, NFE2 | Yes | Dyserythropoiesis |
| GFI1B | 9q34.13 | BCLXL, SOCS1, SOCS3, CDKN1A, GATA3, MEIS1, RAG1/2 | Yes | Red cell aniso/poikilocytosis |
| ETV6 | 12p13 | PF4 | Unknown | Dyserythropoiesis; Increased risk of ALL |
| EVI1 | 3q26.12 | RBM8A, MPL, ITGA2B, ITGB3 | Unknown | BM failure |
| HOXA11 | 7p15.2 | Unknown | BM failure |
ALL, acute lymphoblastic leukemia; ALOX12, 12-lipoxygenase; AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; MYL9, platelet myosin light chain; PCTP, phosphatidylcholine transfer protein; PF4, platelet factor 4; PLDN, pallidin; PRKCQ, protein kinase C-θ.
All of the TF mutations have been associated with variable thrombocytopenia. Platelet count may be normal, as seen in some patients with mutations in RUNX1 or FLI1. Thrombocytopenia may be particularly severe in patients with mutations in GATA1, ETV6, EVI1, and HOXA11 (platelet count <20 × 109/L). Abnormalities in platelet morphology, especially in AGs and DGs, and in aggregation and secretion responses on platelet activation have been described in association with mutations in RUNX1, FLI1, GATA1, and GFI1B. These abnormalities are described in the text and, for RUNX1, shown in Figure 2.