Involvement of CD34+ Stem Cells in Malignant Transformation in AML and MDS — Genetic Analysis of Sorted Subpopulations by Classical and Molecular Cytogenetics

  • D. Haase
  • M. Feuring-Buske
  • C. Schoch
  • C. Schäfer
  • F. Griesinger
  • C. Troff
  • B. Gahn
  • W. Hiddemann
  • B. Wörmann
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 39)

Abstract

In this study we addressed the question whether hematopoietic stem cells characterized by the expression of CD34 are involved in the leukemogenic process in AML and MDS. For this purpose bone marrow cells were sorted according to their expression of CD34 and coexpression of CD38 or CD117 (stem cell factor receptor = CKIT). The sorted subpopulations were genetically analyzed either by cytogenetics or FISH. Successful cytogenetics of sorted CD34+ subpopulations could be performed in 24/54 pts. included in our study (AML: n = 18, MDS: n = 6). At diagnosis 18 displayed a wide variety of different clonal karyotype abnormalities in the unsorted bone marrow: add(2q); +4; 5q−; 5q− and complex anomalies; t(6;9); 6p−; −7; +8; t(8;21); −12; inv(16); i(17q); t(17;20); −21; i(21q). We analyzed sorted stem cell subpopulations with the immunophenotype CD34+/CD38± in 19 pts., in 5 pts. stem cells with the immunophenotype CD34+/ CD117± were examined. We found genetically abnormal stem cells in every subpopulation (CD34+/CD 38−, CD34+/CD38+, CD34+/CD117−, CD34+/CD117−) in every informative case (abnormal karyotype in the unsorted bone marrow and metaphases/interphase cells available for cytogenetic analysis). In 11 pts. a mosaic of normal and abnormal cells was observed in the sorted stem cell subpopulations. In five pts. secondary, progression-associated anomalies were present in the sorted stem cells. We conclude that in AML and MDS malignant transformation and disease progression occur at the level of immature hematopoietic stem cells independent from the phenotype of the leukemic bulk population and the type of genetic alteration.

Keywords

Stem cells AML MDS Chromosomes Cytogenetics CD34 CD38 CD 117 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • D. Haase
    • 1
  • M. Feuring-Buske
    • 1
  • C. Schoch
    • 1
  • C. Schäfer
    • 1
  • F. Griesinger
    • 1
  • C. Troff
    • 1
  • B. Gahn
    • 1
  • W. Hiddemann
    • 1
  • B. Wörmann
    • 1
  1. 1.Dept. of Hematology and OncologyGeorg-August-UniversityGöttingenGermany

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