Elevated frequencies of leukemic myeloid and plasmacytoid dendritic cells in acute myeloid leukemia with the FLT3 internal tandem duplication
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Mareike Rickmann & Juergen Krauter & Kathrin Stamer & Michael Heuser & Gustavo Salguero & Eva Mischak-Weissinger & Arnold Ganser & Renata Stripecke
- چاپ و سال / کشور: 2011
Description
Some 30% of acute myeloid leukemia (AML) patients display an internal tandem duplication (ITD) mutation in the FMS-like tyrosine kinase 3 (FLT3) gene. FLT3-ITDs are known to drive hematopoietic stem cells towards FLT3 ligand independent growth, but the effects on dendritic cell (DC) differentiation during leukemogenesis are not clear. We compared the frequency of cells with immunophenotype of myeloid DC (mDC: Lin−, HLA-DR+, CD11c+, CD86+) and plasmacytoid DC (pDC: Lin−, HLADR+, CD123+, CD86+) in diagnostic samples of 47 FLT3- ITD− and 40 FLT3-ITD+ AML patients. The majority of ITD+ AML samples showed high frequencies of mDCs or pDCs, with significantly decreased HLA-DR expression compared with DCs detectable in ITD− AML samples. Interestingly, mDCs and pDCs sorted out from ITD+ AML samples contained the ITD insert revealing their leukemic origin and, upon ex vivo culture with cytokines, they acquired DC morphology. Notably, mDC/pDCs were detectable concurrently with single lineage mDCs and pDCs in all ITD+ AML (n=11) and ITD− AML (n=12) samples analyzed for mixed lineage DCs (Lin−, HLA-DR+, CD11c+, CD123+). ITD+ AML mDCs/pDCs could be only partially activated with CD40L and CpG for production of IFN-α, TNF-α, and IL-1α, which may affect the antileukemia immune surveillance in the course of disease progression.
Ann Hematol (2011) 90:1047–1058 DOI 10.1007/s00277-011-1231-2 Received: 22 March 2011 / Accepted: 27 March 2011 / Published online: 26 April 2011
