Figure 1.
Deficiency of PLEKHM1 in the BMM accelerates B-ALL disease. (A) Leukocyte counts in PB of WT (red) or Plekhm1 KO (blue) recipient mice on day 20 after transplantation with BCR-ABL1+-transduced BM in the B-ALL model (WT n =16; Plekhm1 KO n = 17; t test). (B) Percentage of GFP+ (BCR-ABL1+) BP-1+ cells of single cells in PB of WT (red) or Plekhm1 KO (blue) recipient mice of BCR-ABL1–transduced BM on day 20 after transplantation. (WT n = 17; Plekhm KO n = 16; test). (C) Kaplan-Meier style survival curve for WT (red solid line) or Plekhm1 KO (blue dashed line) recipient mice with BCR-ABL1+ B-ALL (WT n = 17; Plekhm1 KO n = 18; log-rank test). (D) Percentage of GFP+ (BCR-ABL1+) BP-1+ cells of total leukocytes which homed to the BM or spleen of WT (red) or Plekhm1 KO (blue) recipient mice 18 hours after transplantation (BM: WT n = 5; Plekhm1 KO n = 5; spleen: WT n = 4; Plekhm1 KO n = 4; multiple t tests). (E) Percentage of GFP+ (BCR-ABL1+) BP-1+ early apoptotic (DAPI AnnV) cells of single cells in the BM of WT (red) or Plekhm1 KO (blue) mice with B-ALL on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 5; t test). (F) MFI of CD19 in GFP+ (BCR-ABL1+) cells in the BM of WT (black) or Plekhm1 KO (gray) mice with BCR-ABL1+ B-ALL on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 5; t test). (G) MFI of B220 in GFP+ (BCR-ABL1+) cells in the BM of WT (red) or Plekhm1 KO (blue) mice with BCR-ABL1+ B-ALL on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 5; t test). (H) Relative expression of Pax5 in total BM of WT (red) or Plekhm1 KO (blue) mice with BCR-ABL1+ B-ALL on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 4; t test). (I) Percentage of GFP+ (BCR-ABL1+) BP-1+ cells of single cells in the PB of WT secondary recipient mice of total BM cells from WT (red) or Plekhm1 KO (blue) donor mice with established B-ALL. Cells were analyzed on day 20 after transplantation (WT n = 5; Plekhm1 KO n = 4; t test). (J) Kaplan-Meier style survival curve of WT secondary recipients of total BM cells from WT (red solid line) or Plekhm1 KO (blue dashed line) donor mice with established B-ALL (WT n = 16; Plekhm1 KO n = 17; log-rank test). (K) Percentage of GFP+ (BCR-ABL1+) BP1+ cells of single cells in the BM of WT secondary recipients of total BM cells from WT (red) or Plekhm1 KO (blue) donor mice with established B-ALL. Cells were analyzed on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 6; t test). (L) Percentage of GFP+ (BCR-ABL1+) BP-1+ cells of single cells in the G1, S, or G2 phases of the cell cycle in the BM of WT secondary recipients of total BM cells from WT (red) or Plekhm1 KO (blue) donor mice with established B-ALL. Cells were analyzed on day 20 after transplantation (WT n = 5; Plekhm1 KO n = 6; two-way ANOVA, Sidak multiple comparisons test). (M) Percentage of GFP+ (BCR-ABL1+) BP-1+ early apoptotic (DAPI− AnnV+) cells of single cells in the BM of WT secondary recipients of total BM cells from WT (red) or Plekhm1 KO (blue) donor mice with established B-ALL. Cells were analyzed on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 5; t test). (N) Percentage of GFP+ (BCR-ABL1+) BP1+ late apoptotic (DAPI+ AnnV+) cells of single cells in the BM of WT secondary recipients of total BM cells from WT (red) or Plekhm1 KO (blue) donor mice with established B-ALL. Cells were analyzed on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 5; t test). DAPI, 4′,6-diamidino-2-phenylindole; MFI, mean fluorescence intensity; PB, peripheral blood.

Deficiency of PLEKHM1 in the BMM accelerates B-ALL disease. (A) Leukocyte counts in PB of WT (red) or Plekhm1 KO (blue) recipient mice on day 20 after transplantation with BCR-ABL1+-transduced BM in the B-ALL model (WT n =16; Plekhm1 KO n = 17; t test). (B) Percentage of GFP+ (BCR-ABL1+) BP-1+ cells of single cells in PB of WT (red) or Plekhm1 KO (blue) recipient mice of BCR-ABL1–transduced BM on day 20 after transplantation. (WT n = 17; Plekhm KO n = 16; test). (C) Kaplan-Meier style survival curve for WT (red solid line) or Plekhm1 KO (blue dashed line) recipient mice with BCR-ABL1+ B-ALL (WT n = 17; Plekhm1 KO n = 18; log-rank test). (D) Percentage of GFP+ (BCR-ABL1+) BP-1+ cells of total leukocytes which homed to the BM or spleen of WT (red) or Plekhm1 KO (blue) recipient mice 18 hours after transplantation (BM: WT n = 5; Plekhm1 KO n = 5; spleen: WT n = 4; Plekhm1 KO n = 4; multiple t tests). (E) Percentage of GFP+ (BCR-ABL1+) BP-1+ early apoptotic (DAPI AnnV) cells of single cells in the BM of WT (red) or Plekhm1 KO (blue) mice with B-ALL on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 5; t test). (F) MFI of CD19 in GFP+ (BCR-ABL1+) cells in the BM of WT (black) or Plekhm1 KO (gray) mice with BCR-ABL1+ B-ALL on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 5; t test). (G) MFI of B220 in GFP+ (BCR-ABL1+) cells in the BM of WT (red) or Plekhm1 KO (blue) mice with BCR-ABL1+ B-ALL on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 5; t test). (H) Relative expression of Pax5 in total BM of WT (red) or Plekhm1 KO (blue) mice with BCR-ABL1+ B-ALL on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 4; t test). (I) Percentage of GFP+ (BCR-ABL1+) BP-1+ cells of single cells in the PB of WT secondary recipient mice of total BM cells from WT (red) or Plekhm1 KO (blue) donor mice with established B-ALL. Cells were analyzed on day 20 after transplantation (WT n = 5; Plekhm1 KO n = 4; t test). (J) Kaplan-Meier style survival curve of WT secondary recipients of total BM cells from WT (red solid line) or Plekhm1 KO (blue dashed line) donor mice with established B-ALL (WT n = 16; Plekhm1 KO n = 17; log-rank test). (K) Percentage of GFP+ (BCR-ABL1+) BP1+ cells of single cells in the BM of WT secondary recipients of total BM cells from WT (red) or Plekhm1 KO (blue) donor mice with established B-ALL. Cells were analyzed on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 6; t test). (L) Percentage of GFP+ (BCR-ABL1+) BP-1+ cells of single cells in the G1, S, or G2 phases of the cell cycle in the BM of WT secondary recipients of total BM cells from WT (red) or Plekhm1 KO (blue) donor mice with established B-ALL. Cells were analyzed on day 20 after transplantation (WT n = 5; Plekhm1 KO n = 6; two-way ANOVA, Sidak multiple comparisons test). (M) Percentage of GFP+ (BCR-ABL1+) BP-1+ early apoptotic (DAPI AnnV+) cells of single cells in the BM of WT secondary recipients of total BM cells from WT (red) or Plekhm1 KO (blue) donor mice with established B-ALL. Cells were analyzed on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 5; t test). (N) Percentage of GFP+ (BCR-ABL1+) BP1+ late apoptotic (DAPI+ AnnV+) cells of single cells in the BM of WT secondary recipients of total BM cells from WT (red) or Plekhm1 KO (blue) donor mice with established B-ALL. Cells were analyzed on day 20 after transplantation (WT n = 4; Plekhm1 KO n = 5; t test). DAPI, 4′,6-diamidino-2-phenylindole; MFI, mean fluorescence intensity; PB, peripheral blood.

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