Figure 3. ABCA1 Mutants Support Tet2-Deficient HSPC Expansion and Myeloid Lineage Commitment and Spreads CMML-like Disease in Serial BM Transplantation.

(A and B) Quantification of hematopoietic stem (A) and progenitor (B) cells in the BM of recipient mice transplanted with control or Mx1-Cre⁺Tet2^fl/fl BM expressing empty, ABCA1-WT, or ABCA1 mutants. Lineage(Lin)⁻ Sca1⁻c-Kit⁺ LSK cells are hematopoietic stem and progenitor cells (HSPCs); Lin^_Sca1⁻ c-Kit⁺CD34^hiFcγR^hi are granulocyte-monocyte progenitors (GMPs); and Lin⁻Sca1⁻c-Kit⁺CD34^hiFcγR^low are common myeloid progenitors (CMPs). The results are the means ± SEMs of 5–9 animals per group.

(C and D) The quantification of hematopoietic progenitors (C) and myeloid cells (D) in BM cultures isolated from Mx1-Cre⁺Tet2^fl/fl BM expressing empty, ABCA1-WT, or ABCA1 mutants and grown ex vivo for 72 h in liquid culture in the presence or absence of 6 ng/mL IL-3 and 2 ng/mL GM-CSF. The results are the means ± SEMs of experiments performed in triplicate.

(E) Experimental overview. BM from WT and ABCA1 mutant-transduced animals on aTet2-deficient background were serially transplanted into lethally irradiated WT mice and analyzed 7 weeks later.

(F) Quantification of the percentage of peripheral blood CD11b^hi,Gr-1^hi myeloid cells was determined by flow cytometry at the end of the study period. The results are means ± SEMs.

*p < 0.05 versus empty control transduced animals on a Tet2-deficient background. §p < 0.05 versus ABCA1-WT. #p < 0.05 and ##p < 0.001 versus Mx1-Cre⁺ controls.