MS4A3low is a common feature of CML blastic transformation, primitive leukemic stem cell, and primary TKI resistance. (A) Meta-analysis with transcriptomic datasets comparing CP-CML vs BP-CML (CD34+),13 long CP (>3 years) vs short CP (≤3 years) (CD34+),12 LSCs vs HSCs (CD34+CD38−),41 imatinib responders vs nonresponders (pretherapy CD34+),14 proliferating (CD34+Hoechst+/Pyronine+) vs quiescent (CD34+Hoechstlo/Pyroninelo)40 CML cells. Venn diagram shows the number of genes with a >1.5-fold expression difference. (B) MS4A3 expression on a hierarchical differentiation tree, based on BloodSpot42 illustration of the dataset GSE24759.82 (C) MS4A3 mRNA was quantified by qRT-PCR in CD34+ cells from normal CB (n = 4), adult BM (from femoral head, n = 2), CP-CML (n = 13), BP-CML (n = 4), or TKI-resistant (TKI-R, n = 3) CP-CML patients with unmutated BCR-ABL1. Data were normalized to FH controls. (D) MS4A3 expression was quantified by Affymetrix HG-U133A arrays in 2 independent datasets comparing CD34+ cells from CP-CML (n = 7) and BP-CML (n = 7) patients.53 (E) Flow cytometry analysis of MS4S3 in CB, adult BM, and CP-CML samples (n = 3). (F) OS of CP-CML (n = 35) patients with MS4A3 mRNA expression in CD34+ cells (prior to imatinib therapy) above (high, n = 21) or below (low, n = 14) the value at a bimodal separation. *P < .05, **P < .01, ***P < .001.