Loss of KLF4 impairs the maintenance of BCR-ABL1–induced CML-like disease. (A) KLF4 expression in normal and leukemic stem (CD34⁺ CD38⁻ ALDH^hi) and progenitor (CD34⁺ CD38⁺) cells (n = 5, mean ± standard deviation [SD]) was analyzed using published data (GSE43754). (B) LSK CD150⁺ cells from Klf4^fl/fl (fl/fl) or Klf4^Δ/Δ (Δ/Δ) mice were transduced with retrovirus containing BCR-ABL1-p210 and GFP and transplanted with radioprotective bone marrow (BM) into wild-type recipient mice to induce CML-like myeloproliferative neoplasia. (C) The expansion of myeloid leukemia cells (GFP⁺ CD11b⁺) in peripheral blood (fl/fl, n = 10; Δ/Δ, n = 10). (D) Kaplan-Meier analysis of survival in 2 representative experiments. (E) Immunophenotype of leukemic cells at 20 dpt and moribund mice. (F) LSK CD150⁺ cells from Klf4^fl/fl (fl/fl) or Klf4^fl/flRosa-CreER⁺ (Δ/Δ) mice were transduced with retrovirus containing BCR-ABL1-p210 and GFP and transplanted into wild-type recipient mice to induce gene deletion at 7 dpt. (G) Survival of leukemic mice after tamoxifen (Tam) injection in both groups (fl/fl, n = 7; iΔ/Δ, n = 4). Immunophenotype of leukemia in diseased mice is also shown (right panel). (H) Representative flow cytometric analysis of CML LSCs, defined as GFP⁺ Lin⁻ Sca-1⁺ c-Kit⁺ (GFP⁺ LSK) cells and GFP⁺ LSK Flt3⁻ cells, in the bone marrow of Klf4^fl/fl (fl/fl) or Klf4^fl/flVav-iCre⁺ (Δ/Δ) leukemic mice at 18 dpt (n = 5). (I) Enumeration of GFP⁺ LSK and GFP⁺ LSK Flt3⁻ cells in the bone marrow (BM) and spleen of Klf4^fl/fl or Klf4^Δ/Δ CML mice (n = 5, mean ± SD). The data shown are representative of 3 independent experiments. *P < .05, **P < .01, ****P < .0001, 2-tailed Student t test. BMT, bone marrow transplantation; HPC, hematopoietic progenitor cells; iΔ/Δ, inducible Δ/Δ; LPC, leukemia progenitor cells.