Conditional deletion of Myb at 2 or 12 months determines that the disease is HSC intrinsic. (A) Schematic depicting the Tamoxifen treatment of Myb^+/+:CreER^T2:mTmG (Myb^+/+) and Myb^+/F:CreER^T2:mTmG (Myb^+/F) mice at either at 2 or 12 months of age. (B) Quantitative PCR on peripheral blood genomic DNA, detecting the relative levels of Myb^ex5 product relative to an internal control GpIIb calculated using the ΔCT method. Values represent the mean expression plotted as 2^−ΔCT with SEM (n = 10 P = .020). (C) Kaplan-Meier curve of the survival over 22 months of Myb^+/+ and Myb^+/F mice after Myb deletion at 2 or 12 months of age. The arrows signify the average time from Tamoxifen deletion until disease appearance. Significance was calculated using the log rank test with P = .026 and .006 for the 2– and 12–month deleted Myb, respectively. n = 10 for Myb^+/+ 2- and 12-months, n = 11 for Myb^+/F 2-months, n = 10 for Myb^+/F 12-months. (D) Classification of myeloid disease arising in the aging cohorts of Myb-deleted mice. (E) Absolute bone marrow cell numbers based on antibody staining and total bone marrow count. n = 10 for Myb^+/+ 2- and 12-months, n = 11 for Myb^+/F 2-months, n = 10 for Myb^+/F 2- months. Significance was calculated by t test. (i) KSL^12mP = .032. (ii) MEP^2mP = .052, CMP^2mP =.023, CMP^12mP = .014, GMP^12mP = .031. (iii) Prog^2mP = .052, Prog^12mP = .047. (iv) Monocytes^12mP = .028, (v) Granulocytes^2mP = .032. CMP, common myeloid progenitor; GMP, granulocyte-monocyte progenitor; granulocytes, CD11b⁺Gr1⁺; MEP, megakaryocyte-erythroid progenitor; myeloid progenitors, Kit⁺Sca⁻Lin⁻; monocytes, CD11b⁺Gr1⁻; SEM, standard error of the mean.