The proliferation index of specific bone marrow cell compartments from myelodysplastic syndromes is associated with the diagnostic and patient outcome

• Published in: PloS one 2012-08, Vol.7 (8), p.e44321
• Main Authors: Matarraz, Sergio, Teodosio, Cristina, Fernandez, Carlos, Albors, Manuel, Jara-Acevedo, María, López, Antonio, Gonzalez-Gonzalez, María, Gutierrez, María Laura, Flores-Montero, Juan, Cerveró, Carlos, Pizarro-Perea, Marlies, Paz Garrastazul, María, Caballero, Gonzalo, Gutierrez, Oliver, Mendez, Guy Daniel, González-Silva, Manuel, Laranjeira, Paula, Orfao, Alberto
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Adult; Aged; Aged, 80 and over; Antigens, CD34 - metabolism; Apoptosis; Biology; Blood cells; Bone marrow; Bone Marrow Cells - pathology; Care and treatment; CD34 antigen; Cell Compartmentation; Cell Cycle; Cell Proliferation; Cell Transformation, Neoplastic - pathology; Compartments; Cytogenetic Analysis; Cytogenetics; Cytometry; Deoxyribonucleic acid; Development and progression; Diagnosis; Diagnostic systems; Disease Progression; Disorders; DNA; Epigenetics; Erythrocytes; Erythrocytes - pathology; Failure analysis; Female; Flow cytometry; Gene expression; Genetic aspects; Hematopoiesis; Hematopoietic Stem Cells - pathology; Hemopoiesis; Humans; Leukemia; Leukemia, Myeloid, Acute - pathology; Leukocytes (neutrophilic); Male; Medical diagnosis; Medical prognosis; Medicine; Middle Aged; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - blood; Myelodysplastic Syndromes - classification; Myelodysplastic Syndromes - diagnosis; Myelodysplastic Syndromes - pathology; Myeloid leukemia; Neutrophils; Patients; Physiological aspects; Risk; Stem cells; Studies; Survival Analysis; Transformation; Treatment Outcome
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0044321

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.