The aorta-gonad-mesonephros-derived stroma cell line DAS104-4 induces differentiation of leukemic cells.
While critical steps in the regulation of leukemia cell development have been intensively studied in recent years, less is known about the interactions of leukemic cells with their stroma. Previously, we have shown that human acute myeloid leukemia (AML) cells differentiate upon injection into murine blastocysts. We here describe that human AML Kasumi-1 cells, cocultured with murine aorta-gonad-mesonephros (AGM) region-derived DAS104-4 stromal cells, decrease proliferation and colony formation efficiency; and up-regulate myelo-monocytic cell surface markers. Gene expression analysis showed decreased transcription of the AML1-ETO fusion gene and increased transcription of p16 (INK4A), p21 (WAF1) and C/EBPalpha genes. Coculture can induce myeloid differentiation also in patient-derived AML cells. Our findings strengthen the notion that the embryonic milieu can regulate the proliferation and differentiation of leukemic cells.
Pramanik
Kallal
K
Institut für Medizinische Strahlenkunde und Zellforschung (MSZ), Universität Würzburg, Versbacherstr. 5, D-97078 Würzburg, Germany.
Trüpschuch
Sandra
S
Greiner
Axel
A
Ruthardt
Martin
M
Henschler
Reinhard
R
Müller
Albrecht M
AM
D001011:Aorta / Q000166:cytology / Q000196:embryology*; D039481:CD11b Antigen / Q000032:analysis; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D018920:Coculture Techniques; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D006066:Gonads / Q000166:cytology / Q000196:embryology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008650:Mesonephros / Q000166:cytology / Q000196:embryology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D000075142:RUNX1 Translocation Partner 1 Protein; D017154:Stromal Cells / Q000502:physiology*
C107844:AML1-ETO fusion protein, human; D039481:CD11b Antigen; D050676:Core Binding Factor Alpha 2 Subunit; C509295:ITGAM protein, human; D018950:Lipopolysaccharide Receptors; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein