title: Cytogenetic analysis of CD34+ subpopulations in AML and MDS characterized by the expression of CD38 and CD117.
abstract: It has been supposed in de novo AML that malignant transformation occurs at the level of committed progenitors. Recent data of our group and others provide evidence that in AML malignant transformation may regularly occur at the level of stem cells. These cells can be discriminated by function and specific surface molecules. CD34, a glycophosphoprotein, is a cellular surface antigen characteristically expressed by stem cells. CD34+ stem cells can be further subdivided by the expression of additional surface molecules like CD38 and CD117. In this article we present results from cytogenetic examinations of FACS-isolated stem cell subpopulations in eight patients (four AML and four MDS). Six of them displayed clonal karyotype abnormalities at the time of first diagnoses in the native bone marrow (5q-; 5q- and complex abnormalities; +8; inv(16) and +8; i(17q) and -21; i(21q)). We used CD117, the receptor for the stem cell factor (also KIT oncogene) as a new cellular surface marker. CD34+/CD117+/- stem cell subpopulations were examined in two patients with AML and three patients with MDS. We found leukemic stem cells in every type of stem cell subpopulation examined (CD34+/CD38-, CD34+/CD38+, CD34+/CD117-, CD34+/CD117+). Secondary, progression-associated chromosome abnormalities likewise were demonstrable in CD34+ cells. In three patients a mosaic of normal and abnormal metaphases was found in the highly purified stem cell subpopulations. We conclude that in AML and MDS stem cells are the target of leukemogenic genetic defects. CD117 as a new marker to isolate different CD34+ subpopulations was not sufficient to discriminate between normal and leukemic stem cells. Our findings have implications for autologous stem cell transplantation, high-dose chemotherapy and the pathogenetic concept of leukemogenesis.
authors.affiliation: Department of Internal Medicine, Georg-August-University, Göttingen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Haase
authors.forename: M
authors.initials: M
authors.lastname: Feuring-Buske
authors.forename: C
authors.initials: C
authors.lastname: Schäfer
authors.forename: C
authors.initials: C
authors.lastname: Schoch
authors.forename: C
authors.initials: C
authors.lastname: Troff
authors.forename: B
authors.initials: B
authors.lastname: Gahn
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
authors.forename: B
authors.initials: B
authors.lastname: Wörmann
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis* / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000032:analysis*; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology*; D002471:Cell Transformation, Neoplastic; D002503:Centromere; D002898:Chromosomes, Human, Pair 8; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D008954:Models, Biological; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D009699:N-Glycosyl Hydrolases / Q000096:biosynthesis*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D019009:Proto-Oncogene Proteins c-kit; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1