(A–D) Gene expression data from sorted MDS/AML bone marrow samples were compared with data from healthy controls (Ctrl) and revealed significantly increased STAT3 expression in LT-HSCs (Lin–, CD34+, CD38–, CD90–, n = 12 MDS/AML, healthy control [HC] = 4), ST-HSCs (Lin–, CD34+, CD38–, CD90), and GMPs (Lin–, CD34+, CD38+, CD90+, CD123+) (P < 0.001, FDR < 5%). (E and F) Cytogenetic abnormalities are depicted as: NK, normal karyotype; CK, complex karyotype; –7, deletion of chromosome 7. “Ctrl” refers to healthy control sorted populations. qPCR on an independent cohort of sorted cells from controls and MDS and AML samples reveals increased expression of STAT3 in MDS/AML HSCs (LT/ST) and GMPs. (G) Survival of 183 MDS patients was correlated with STAT3 expression in marrow-derived CD34+ cells. Patients with higher STAT3 levels (greater than median) had a median survival of 2.6 years compared with 5.8 years for the group with lower STAT3 (log-rank P < 0.01). (H–J) Patients with high STAT3 expression also had significantly reduced mean hemoglobin levels, a higher blast percentage, and increased transfusion dependence. Test of proportions, *P < 0.05.