The dominant clone establishes disease upon secondary transfer. Secondary transplantation of 1 × 10⁶ primary bone marrow and/or spleen cells from Dnmt3a-KO primary diseased mice. (A) Kaplan-Meier survival curve of secondary recipient mice. All secondary recipients of bone marrow (n = 4) and spleen (n = 4, 4) cells from primary Dnmt3a-KO AML developed fatal AML within 124 days. Transplantation of bone marrow from 5 primary Dnmt3a-KO MDS samples also generated MDS in secondary mice (n = 4 recipients per tumor). Transplantation of bone marrow and/or spleen from 2 mixed MDS/AML primary samples generated AML in secondary recipients with long latency (n = 4, 8). (B) Peripheral blood smears of an individual Dnmt3a-KO tumor at time of sacrifice in primary and secondary recipients. Sample showed MDS characteristics in the blood of primary recipients (insets: lower left shows Howell-Jolly body, and upper right shows abnormal nucleated neutrophil), but blood of secondary recipient was packed with myeloid blasts (upper right inset; white blood cell [WBC] count >200 K/μL). Scale bar represents 10 μm. (C) WBC counts at time of sacrifice of individual tumors in primary and secondary recipients. For each paired sample, the black square is WBC count of primary tumor used as the donor for secondary transplant. Open circles are WBC count at time of sacrifice in secondary mice. Dnmt3a-KO MDS samples produced the same disease in primary and secondary mice.