Altered frequencies of PB HSPCs in patients with CLL. (A-C) Absolute numbers of global (CD34⁺) hematopoietic progenitors from nonpurified peripheral blood mononuclear cells isolated from PB. (A) Comparison between aged-matched controls (n = 20) and patients with CLL (n = 54) is shown. Unpaired Student t test. (B) Quantification of CD34⁺ cells in treatment-naive patients, separated by Binet stage (ordinary 1-way analysis of variance [ANOVA] followed by unpaired Student t tests). Binet stage, A = 25; B = 11; C = 4. (C) Abundance of CD34⁺ progenitors in the CLL cohort by treatment type (ordinary 1-way ANOVA followed by unpaired Student t tests). Controls, N = 20; naive patients with CLL, n = 40; ibrutinib-treated, n = 3; previously treated, n = 11. (D) Representative fluorescence-activated cell sorting plots of CMPs-MEPs and ST-HSC abundance of freshly isolated CD34⁺ cells. Values indicate abundance of the specific population, as relative frequency of total CD34⁺ pool. (E) Dot-plot showing relative abundance of specific hematopoietic progenitors in healthy controls (n = 20) and the entire patient cohort (n = 89) (unpaired Student t test controls). (F) Dot-plot showing relative abundance of specific hematopoietic progenitors in healthy controls (n = 20) and in patients with CLL by treatment group (ordinary 1-way ANOVA); naive patients, n = 66; previously treated patients, n = 23. (G) Linear regression plots showing correlation of ST-HSC frequencies (as %CD34⁺) to white blood cell counts in naive patients (n = 58) (above), and previously treated patients (n = 15) (below). P values from unpaired Student t tests or 1-way ANOVA are denoted with asterisks according to the following: ****P < .0001, ***P < .001, **P < .01, *P < .05. GMP, granulocyte monocyte progenitors; B-NK, B-NK progenitors; WBC, white blood cell.