title: Cell-cycle distribution of different cell compartments in normal versus reactive bone marrow: a frame of reference for the study of dysplastic hematopoiesis.
abstract: Limited information is currently available about the proliferation activity and cell-cycle distribution of different bone marrow (BM) cell subsets defined according to their lineage and maturation stage in normal versus cytopenia-associated reactive BM samples. Here, we report a three-color flow cytometry approach to investigate the cell-cycle distribution of different BM cell compartments-CD34(+) hematopoietic progenitor and precursor cells (HPC), maturing neutrophils and monocytic cells, mature lymphocytes, eosinophils, and nucleated red blood cell precursors (NRBC)-from normal (n = 47) versus cytopenia-associated reactive (n = 47) BM samples. Highly similar proliferation profiles were detected in normal versus reactive BM, with a higher proliferation index (PI) for the more immature CD34(+) HPC, CD11b(-) maturing neutrophils and NRBC versus other BM cell compartments. The only differences observed between normal and reactive BM were restricted to the more mature (CD13(hi) /CD11b(+) ) bands/neutrophils and to monocytic cells, which showed an increased PI (0.9% ± 0.8% vs. 0.6% ± 0.5% and 6 ± 3.6 vs. 4.6 ± 4.5, respectively) at the expense of a lower PI of CD34(+) HPC in reactive conditions. Of note, bands/mature neutrophils and mature lymphocytes showed either residual numbers or absence of S + G₂ /M-phase cells in both normal and reactive BM. Our results suggest that a slight shift of proliferation from the early precursors to the more mature granulomonocytic compartment occurs in reactive BM, which could reflect an attempt of the hematopoietic system to rapidly produce functional neutrophils and monocytes, at the expense of a lower expansion of the minor compartments of CD34(+) HPC.
authors.affiliation: Servicio de Citometría and Departamento de Medicina, Centro de Investigación del Cáncer, Instituto de Biología Celular y Molecular del Cáncer, CSIC-USAL, Universidad de Salamanca, Salamanca, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Matarraz
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez
authors.forename: Manuel
authors.initials: M
authors.lastname: Albors
authors.forename: Cristina
authors.initials: C
authors.lastname: Teodosio
authors.forename: Antonio
authors.initials: A
authors.lastname: López
authors.forename: María
authors.initials: M
authors.lastname: Jara-Acevedo
authors.forename: Carlos
authors.initials: C
authors.lastname: Cervero
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Caballero
authors.forename: Oliver
authors.initials: O
authors.lastname: Gutierrez
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000368:Aged; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000175:diagnosis; D001854:Bone Marrow Cells / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D001855:Bone Marrow Diseases / Q000097:blood / Q000175:diagnosis*; D049109:Cell Proliferation; D002877:Chromosomes, Human / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D013997:Time Factors