The t(6;9) associated DEK/CAN fusion protein targets a population of long-term repopulating hematopoietic stem cells for leukemogenic transformation.
The t(6;9)-positive acute myeloid leukemia (AML) is classified as a separate clinical entity because of its early onset and poor prognosis. The hallmark of t(6;9) AML is the expression of the DEK/CAN fusion protein. The leukemogenic potential of DEK/CAN has been called into question, because it was shown to be unable to block the differentiation of hematopoietic progenitors. We found that DEK/CAN initiated leukemia from a small subpopulation within the hematopoietic stem cell (HSC) population expressing a surface marker pattern of long-term (LT) HSC. The propagation of established DEK/CAN-positive leukemia was not restricted to the LT-HSC population, but occurred even from more mature and heterogeneous cell populations. This finding indicates that in DEK/CAN-induced leukemia, there is a difference between 'leukemia-initiating cells' (L-ICs) and 'leukemia-maintaining cells' (L-MCs). In contrast to the L-IC cells represented by a very rare subpopulation of LT-HSC, the L-MC seem to be represented by a larger and phenotypically heterogeneous cell population.
Oancea
C
C
Department of Hematology, Goethe University, Frankfurt, Germany.
Rüster
B
B
Henschler
R
R
Puccetti
E
E
Ruthardt
M
M
D000818:Animals; D000950:Antigens, Ly / Q000235:genetics; D002454:Cell Differentiation; D003114:Colony-Forming Units Assay; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D007942:Leukemia, Experimental / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016297:Mutagenesis, Site-Directed; D028861:Nuclear Pore Complex Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics*; D016366:Open Reading Frames; D000075223:Poly-ADP-Ribose Binding Proteins; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013163:Splenomegaly / Q000473:pathology; D014178:Translocation, Genetic
D000950:Antigens, Ly; C519564:DEK protein, mouse; D004268:DNA-Binding Proteins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D028861:Nuclear Pore Complex Proteins; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011993:Recombinant Fusion Proteins