title: CD34+ cells from acute myeloid leukemia, myelodysplastic syndromes, and normal bone marrow display different apoptosis and drug resistance-associated phenotypes.
abstract: Myelodysplastic syndromes and acute myeloid leukemia (AML) are heterogeneous disorders in which conflicting results in apoptosis and multidrug resistance (MDR) have been reported. We have evaluated by multiparameter flow cytometry the expression of apoptosis- (APO2.7, bcl-2, and bax) and MDR-related proteins [P-glycoprotein (P-gp), multidrug resistance protein (MRP), and lung resistance protein (LRP)] specifically on bone marrow (BM) CD34+ cells, and their major CD32-/dim and CD32+ subsets, in de novo AML (n=90), high-risk myelodysplastic syndrome (n=9), and low-risk myelodysplastic syndrome (n=21) patients at diagnosis, and compared with normal BM CD34+ cells (n=6). CD34+ myeloid cells from AML and high-risk myelodysplastic syndrome patients displayed higher expression of bcl-2 (P <0.0001) and lower reactivity for APO2.7 (P=0.002) compared with low-risk myelodysplastic syndrome and normal controls. Similar results applied to the two predefined CD34+ myeloid cell subsets. No significant differences were found in the expression of P-gp, MRP, and LRP between low-risk myelodysplastic syndrome patients and normal BM, but decreased expression of MRP (P <0.03) in AML and high-risk myelodysplastic syndromes and P-gp (P=0.008) in high-risk myelodysplastic syndromes were detected. Hierarchical clustering analysis showed that low-risk myelodysplastic syndrome patients were clustered next to normal BM samples, whereas high-risk myelodysplastic syndromes were clustered together and mixed with the de novo AML patients. In summary, increased resistance to chemotherapy of CD34+ cells from both AML and high-risk myelodysplastic syndromes would be explained more appropriately in terms of an increased antiapoptotic phenotype rather than a MDR phenotype. In low-risk myelodysplastic syndromes abnormally high apoptotic rates would be restricted to the CD34- cell compartments.
authors.affiliation: Department of Hematology, Hospital Universitario, Centro de Investigación del Cáncer, University of Salamanca, Salamanca, Spain.
authors.forename: Lilia
authors.initials: L
authors.lastname: Suárez
authors.forename: María-Belén
authors.initials: MB
authors.lastname: Vidriales
authors.forename: José
authors.initials: J
authors.lastname: García-Laraña
authors.forename: Guillermo
authors.initials: G
authors.lastname: Sanz
authors.forename: María-José
authors.initials: MJ
authors.lastname: Moreno
authors.forename: Antonio
authors.initials: A
authors.lastname: López
authors.forename: Susana
authors.initials: S
authors.lastname: Barrena
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez
authors.forename: Mar
authors.initials: M
authors.lastname: Tormo
authors.forename: Luis
authors.initials: L
authors.lastname: Palomera
authors.forename: Esperanza
authors.initials: E
authors.lastname: Lavilla
authors.forename: Ma Consuelo
authors.initials: MC
authors.lastname: López-Berges
authors.forename: María
authors.initials: M
authors.lastname: de Santiago
authors.forename: M Encarnación Pérez
authors.initials: ME
authors.lastname: de Equiza
authors.forename: Jesús F San
authors.initials: JF
authors.lastname: Miguel
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis*; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism*; D016000:Cluster Analysis; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D009190:Myelodysplastic Syndromes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012306:Risk; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein; D000099187:Major Vault Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018952:Antigens, CD34; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020394:Vault Ribonucleoprotein Particles; D051028:bcl-2-Associated X Protein; D000099187:Major Vault Protein; C494826:BAX protein, human