Figure 1.

Expression of NUP214-ABL1 and TLX1 Is Required to Induce T-ALL in a Transgenic Mouse Model

(A) Pie chart representing the percentage of T-ALL (left) or NUP214-ABL1-positive T-ALL (right) with TLX1 or TLX3 expression.

(B) Schematic overview of the transgenic mouse models used in this study. Red triangles represent LoxP sites. A conditional loxP-STOP-loxP NUP214-ABL1 knockin mouse model (abbreviated as LSL-NA) was generated. NUP214-ABL1 expression was initiated by crossing LSL-NA mice with CD4-Cre mice. Co-expression of NUP214-ABL1 and TLX1 was achieved by crossing NA mice with Tg(Lck-TLX1) mice, resulting in Tg(CD4 Cre; NUP214-ABL1; Lck TLX1) mice (abbreviated as NA + TLX1).

(C) Kaplan-Meier overall survival curve comparing NA + TLX1, TLX1, and NA mice.

(D) Representative fluorescence-activated cell sorting (FACS) analysis of GFP expression in NA + TLX1 mice at end-stage disease compared with wild-type (WT) cells for spleen, thymus, peripheral blood (PB), and bone marrow (BM).

(E–G) Peripheral white blood cell count (WBC) (E), spleen weight (F), and thymus weight (G) at end-stage disease for NA + TLX1 mice compared with NA and LSL-NA mice (end stage for NA and LSL-NA defined as >360 days). Star indicates NA + TLX1 mouse that presented with an elevated WBC, but did not present with an enlarged spleen or thymus at end stage. Statistical significance was calculated using a Mann-Whitney test. Data are presented as mean ± SD. N.s., not significant.

(H) Representative FACS analysis for CD4 and CD8 expression in GFP-positive NA + TLX1 leukemic cells from the peripheral blood compared with NA and LSL-NA peripheral blood cells.

(I) H&E and immunohistochemical staining for CD3 and Cre in spleen cells from LSL-NA, NA, and NA + TLX1 mice. Scale bars represent 100 μm.

(J) Kaplan-Meier overall survival curve of secondary (using cells from three different primary NA + TLX1 mice) and tertiary transplants.

(K) Growth curve of ex vivo primary immature pro T cells expressing EML1-ABL1, TLX1 or both. Data are presented as mean ± SD.

(L) Kaplan-Meier overall survival curve of mice transplanted with hematopoietic stem/progenitor cells expressing EML1-ABL1, TLX1 or EML1-ABL1+TLX1.

See also Figures S1–S4 and Table S1.