Fig. 7. HOXA9 partially rescues survival defects of SYNCRIP depleted cells.

(a) Colony formation was rescued in SYNCRIP-KD dsRed leukemia cells with MSI2 overexpression. n=3 independent experiments. (b) Colony formation was rescued in dsRed SYNCRIP-KD leukemia cells with HOXA9-CDS overexpression. n=4 independent experiments. (c) Immunoblots showing efficient depletion of SYNCRIP expression, protein expression of HOXA9. (d) Cell growth was rescued in SYNCRIP-KD human MOLM13 leukemia cells with HOXA9 overexpression. n=3 independent experiments. (e) Immunoblots showing efficient depletion of SYNCRIP expression, protein expression of HOXA9. (f) Quantitive summary of percentage of engrafted hCD45 GFP cells in recipient mice transplanted with primary AML patient cells transduced with control shRNA or shRNAs against SYNCRIP (shRNA#1 and shRNA#2) at week 10 and week 16 post transplantation. n=5 for each group. (g) Immunoblots showing efficient depletion of SYNCRIP expression in primary AML patient cells and downregulation of HOXA9 expression. All data: error bars, s.e.m. ns:*p<0.05, **p<0.001, ***p<0.0001 two tailed t test. (h) Schematic depicting the dominant function of SYNCRIP when its expression is elevated in LSCs in comparison to normal HSCs. In LSCs, SYNCRIP and MSI2 binds and increases expression of the mRNA transcripts associated with the MLL self-renewal program, including Hoxa9 thus driving the LSCs program instead of normal hematopoietic development.