Mild to moderate thrombocytopenia along with low-normal to normal thrombocyte numbers are possible. Thrombocytopenia is due to disrupted maturation of the megakaryocytes. Dysmegakaryopoiesis is the most common abnormal finding in bone marrow smears.
Thrombocyte size is normal. However, there is a functional defect in most cases, with the most common form being dense-granule storage pool deficiency, a reduction in the dense granules that disrupts the irreversible thrombocyte aggregation. However, other functional defects have also been associated with RUNX1 mutations.
The severity of hemorrhaging resulting from thrombocytopenia and thrombocyte functional defects varies greatly.
The risk of malignant transformation to MDS or AML is 30-40%. Patients carrying a RUNX1 mutation with a dominant negative effect are at greater risk than patients with a haploinsufficient RUNX1 mutation.
Various AML French-American-British (FAB) RUNX1 mutation subtypes have been observed. Refractory anemia with excess blasts, chronic myeloid leukemia, and hypoplastic MDS with myelofibrosis occur with MDS and myeloproliferative neoplasms (MPN). In addition to predominantly affecting the myeloid lineage, it is also possible that the lymphatic lineage is affected, which manifests in the development of T-ALL.
The average age of onset for MDS or AML is 33, although the age range is more extensive. T-ALL associated with a RUNX1 mutation generally occurs at an earlier stage of life.