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NOTCH1 Signaling Promotes Human T-Cell Acute Lymphoblastic Leukemia Initiating Cell Regeneration in Supportive Niches

Figure 5

An expanded CD45⁺CD34⁺CD2⁺CD7⁺ population in NOTCH1^Mutated T-ALL LIC is sensitive to hN1 mAb treatment.

(A) Total human CD45⁺ cells including CD34⁺CD45⁺ and CD34^-CD45⁺ in secondary (2°) transplant recipients were summarized by graphing the results of CD45 FACS analysis. Human cord blood CD34⁺ progenitors were used as a normal progenitor control, where the engraftment of human CD45⁺ cells in bone marrow was 7.13% ±1.3 (n = 6). (B) FACS analysis of pediatric T-ALL engrafted bone marrows revealed an expanded human CD45⁺CD34⁺CD2⁺CD7⁺ population in secondary (2°) transplant recipients that was more prominent in NOTCH1^Mutated T-ALL (Patient 05, n = 9; Patient 08, n = 8; Patient 11, n = 8; Patient 12, n = 3) and NOTCH1^High T-ALL (Patient 02, n = 10) transplanted mice than NOTCH1^WT T-ALL transplanted mice (Patient 09, n = 4; Patient 10, n = 3). Human cord blood CD34⁺ progenitors were used as a normal progenitor control (n = 6). The CD34⁺CD45⁺, CD34⁺CD45⁺CD2⁺CD7⁺, and CD34⁺CD45⁺CD2⁺CD7⁻ populations were significantly higher in the bone marrows of both NOTCH1^Mutated and NOTCH1^High T-ALL LIC transplanted mice (**, P<0.01; ***, P<0.001, Student’s t test) when compared with NOTCH1^WT T-ALL LIC transplanted mice. (C) FACS analysis of pediatric T-ALL LIC (Patient 05, n = 5 in control group, n = 6 in hN1 group; Patient 08, n = 5 in control group, n = 6 in hN1 group; Patient 11, n = 4 in control group, n = 5 in hN1 group) engrafted bone marrows showing a reduction in the human CD45⁺CD34⁺CD2⁺CD7⁺ cell population following hN1 mAb treatment compared to control IgG1 mAb (***, P<0.001, Student’s t test).

doi: https://doi.org/10.1371/journal.pone.0039725.g005