Stroma-derived factors protect AML MNCs from broad-spectrum TKIs. HS-5 CM induces resistance to drugs targeting (A-B) FLT3 and (C-D) PDGFR in samples from patients with AML carrying FLT3-ITD (red-colored samples vs blue-colored samples without the alteration) and/or CCDC88C-PDGFRB alterations (samples 1886_2, 1886_6, 1886_8, 1886_9, green-colored samples). (E-F) Likewise, sensitivity to broad-spectrum TKIs sorafenib and regorafenib is lost in the presence of CM, whereas (G-H) the samples with a FLT3-ITD show increased response to JAK kinase inhibitors ruxolitinib and AZD1480 in the presence of CM.