Fig. 2.

Deficiency of aPKCλ, but not aPKCζ, abrogates the development of B-ALL. a Kaplan–Meier survival analyses of competitively transplanted secondary recipients. Whole BM cells derived from Scl/p210: WT, aPKCζ^−/−, aPKCλ^∆/∆ and DKO chimeric primary recipients along with competitor cells (CD45.1⁺ BoyJ BM cells) were transplanted into B6.SJL.Ptprc^a.Pepc^{b BoyJ} (BoyJ) secondary recipients at 1:1 ratio. Mice were followed for the development of leukemia, and sick and moribund mice were sacrificed. b Donor leukemic chimera (CD45.2⁺ cells) in the PB of secondary recipients at different time interval after transplantation. c Kaplan–Meier survival analyses of competitively transplanted tertiary recipients. Whole BM cells from Scl/p210; WT, aPKCζ^−/−, aPKCλ^Δ/Δ and DKO chimeric secondary recipients transplanted into BoyJ tertiary recipients, and the development of leukemia was followed. d Donor leukemic chimera (CD45.2⁺ cells) in the PB of tertiary recipients at different time interval after transplantation. e Lymphadenopathies (black arrows), hepatomegaly (gray arrows) and splenomegaly (arrowheads) in WT and aPKCζ^−/− chimeric secondary recipient mice. aPKCλ^Δ/Δ and DKO chimeric mice do not show any signs of B-ALL when followed up to 6 months post-transplantation f, g Representative example of spleen images (f) and spleen size (g) of Scl/p210; WT, aPKCζ^−/−, aPKCλ^Δ/Δ and DKO chimeric mice at autopsy. h CFU-pre B content in the BM and spleen. i FACS quantification of leukemic B-cell progenitors in the BM and spleen of secondary recipient chimeric mice at autopsy. Deficiency of aPKCλ results in drastic reduction in leukemic B-cell progenitors content in the BM and spleen. j Q-RT-PCR analyses of p210-BCR-ABL (B3A2) expression in B progenitors derived from primary and secondary recipient chimeric mice. B-cell progenitors derived from secondary recipients show significant upregulation of p210-BCR-ABL expression. k Representative example of western blot of p210-BCR-ABL expression in B-cell progenitors derived from primary and secondary recipient chimeric mice. Data are presented as mean ± SD of a minimum of three independent experiments. *p < 0.05; **p < 0.01; ***p < 0.001, t-test