Figure 2. Tet2 ^H1881R mutation results in a spectrum of myeloid malignancies.

A, Expression levels (measured by RNA-seq) of Tet2 wild-type and H1794R alleles in Tet2^+/HR HSPCs (Lineage^neg Kit⁺ cells).

B, Western blot analysis of Tet2 protein expression from Tet2^+/+, Tet2^+/HR, and Tet2^−/− mice bone marrow cells.

C, Flow cytometry analysis of 5hmC expression levels in Tet2^+/+ and Tet2^+/HR HSPCs (Lineage^neg Kit⁺ cells).

D, Kaplan Meier survival curves of Tet2^WT and Tet2^HR

E, Levels of White Blood Counts (WBC), Monocytes, Red Blood Cells (RBC), Hemoglobin (Hg) and platelets from peripheral blood samples collected from young and old Tet2^HR and control samples

F, Representative flow cytometry analysis plots showing myeloid cell population percentages (Cd11B and GR-1) in peripheral blood of Tet2^WT and Tet2^HR old mice.

G, Percentage of myeloid cells (Cd11B and Gr-1+) in the peripheral blood of Tet2^WT and Tet2^HR mice.

H, Top panel: Tet2^WT old BM shows orderly trilineage hematopoiesis, spleen and liver. Middle panel: In Tet2^HR old, the chronic (mild) phase of disease shows MDS/MPN-like features with proliferation of atypical megakaryocytes and increased myeloid:erythroid ratio; myeloid maturation is preserved. The splenic red pulp is infiltrated by atypical megakaryocytes. The liver was uninvolved. Bottom panel: “transformed” or “severe” disease shows BM involvement by acute myeloid leukemia with sheets of blasts. The splenic red pulp is infiltrated by abnormal megakaryocytes (right half; arrow); in additional nodular aggregate of mononuclear cells is also present, largely replacing normal splenic tissue (myeloid sarcoma); and the liver is also involved by myeloid sarcoma. I, Kaplan Meier curve of sub-lethally irradiated mice transplanted with total bone marrow cells collected from Tet2^HR mice with transformed disease.