title: The proliferation index of specific bone marrow cell compartments from myelodysplastic syndromes is associated with the diagnostic and patient outcome.
abstract: Myelodysplastic syndromes (MDS) are clonal stem cell disorders which frequently show a hypercellular dysplastic bone marrow (BM) associated with inefficient hematopoiesis and peripheral cytopenias due to increased apoptosis and maturation blockades. Currently, little is known about the role of cell proliferation in compensating for the BM failure syndrome and in determining patient outcome. Here, we analyzed the proliferation index (PI) of different compartments of BM hematopoietic cells in 106 MDS patients compared to both normal/reactive BM (n = 94) and acute myeloid leukemia (AML; n = 30 cases) using multiparameter flow cytometry. Our results show abnormally increased overall BM proliferation profiles in MDS which significantly differ between early/low-risk and advanced/high-risk cases. Early/low-risk patients showed increased proliferation of non-lymphoid CD34(+) precursors, maturing neutrophils and nucleated red blood cells (NRBC), while the PI of these compartments of BM precursors progressively fell below normal values towards AML levels in advanced/high-risk MDS. Decreased proliferation of non-lymphoid CD34(+) and NRBC precursors was significantly associated with adverse disease features, shorter overall survival (OS) and transformation to AML, both in the whole series and when low- and high-risk MDS patients were separately considered, the PI of NRBC emerging as the most powerful independent predictor for OS and progression to AML. In conclusion, assessment of the PI of NRBC, and potentially also of other compartments of BM precursors (e.g.: myeloid CD34(+) HPC), could significantly contribute to a better management of MDS.
authors.affiliation: Centro de Investigación del Cáncer (Instituto de Biología Celular y Molecular del Cáncer, CSIC-USAL), IBSAL, Servicio de Citometría and Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Matarraz
authors.forename: Cristina
authors.initials: C
authors.lastname: Teodosio
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernandez
authors.forename: Manuel
authors.initials: M
authors.lastname: Albors
authors.forename: María
authors.initials: M
authors.lastname: Jara-Acevedo
authors.forename: Antonio
authors.initials: A
authors.lastname: López
authors.forename: María
authors.initials: M
authors.lastname: Gonzalez-Gonzalez
authors.forename: María Laura
authors.initials: ML
authors.lastname: Gutierrez
authors.forename: Juan
authors.initials: J
authors.lastname: Flores-Montero
authors.forename: Carlos
authors.initials: C
authors.lastname: Cerveró
authors.forename: Marlies
authors.initials: M
authors.lastname: Pizarro-Perea
authors.forename: María
authors.initials: M
authors.lastname: Paz Garrastazul
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Caballero
authors.forename: Oliver
authors.initials: O
authors.lastname: Gutierrez
authors.forename: Guy Daniel
authors.initials: GD
authors.lastname: Mendez
authors.forename: Manuel
authors.initials: M
authors.lastname: González-Silva
authors.forename: Paula
authors.initials: P
authors.lastname: Laranjeira
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000473:pathology*; D002451:Cell Compartmentation; D002453:Cell Cycle; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D020732:Cytogenetic Analysis; D018450:Disease Progression; D004912:Erythrocytes / Q000473:pathology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000145:classification / Q000175:diagnosis* / Q000473:pathology*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018952:Antigens, CD34