CD34+ leukemic subpopulation predominantly displays lower spontaneous apoptosis and has higher expression levels of Bcl-2 and MDR1 genes than CD34- cells in childhood AML.
In view of obscure clinical and biological significance of leukemic cells heterogeneity, we studied the efficacy of apoptosis, proliferation, and expression levels of the Bcl-2, MDR1, LRP, and BCRP genes in sorted CD34+ and CD34- subpopulations of childhood AML leukemic samples. In five out of nine cases, CD34+ cells were less sensitive to spontaneous apoptosis and had from 1.2- to 5.0-fold higher expression levels of Bcl-2 (eight of ten) and from 1.5- to 28.7-fold higher expression levels of MDR1 (eight of ten). The expression levels of the LRP gene were from 1.1- to 1.8-fold higher in CD34+ subpopulations (five of ten cases), and the expression levels of the BCRP gene were from 1.1- to 22.4-fold higher in CD34+ leukemic cells (six of ten). In all M4 cases, the expression levels of LRP were higher in the CD34- subpopulation. Significant differences in the patterns of genes expression between patients do not allow us to conclude that the CD34+ fractions have more resistant phenotype than the CD34- subpopulations. Nevertheless, distinctions between CD34+ and CD34- cells may lead to different chemosensitivities between leukemic subpopulations in vivo and may determine the alteration of the leukemic immunophenotype during treatment and in relapse.
Shman
Tatsiana V
TV
Belarusian Research Center for Pediatric Oncology and Hematology, Minski distr., Pos. Lesnoe, Minsk, Belarus 223053. t_shman@yahoo.com
Fedasenka
Uladzimir U
UU
Savitski
Valery P
VP
Aleinikova
Olga V
OV
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D018952:Antigens, CD34; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D020869:Gene Expression Profiling; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D016131:Lymphocyte Subsets / Q000145:classification / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D018365:Neoplasm, Residual / Q000378:metabolism / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012008:Recurrence; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D018952:Antigens, CD34; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C116614:ABCG2 protein, human