Modulation of histidine decarboxylase activity and cytokine synthesis in human leukemic cell lines: Relationship with basophilic and/or megakaryocytic differentiation

In the present study, we show that UT7D1 cells, derived from the pluripoten t cell line UT7, express high levels of histidine decarboxylase (HDC) mRNA spontaneously. These cells conserve the ability to differentiate into megak aryocytes upon stimulation with PMA, while greatly increasing their HDC act ivity. We provide evidence that enhanced HDC activity reflects the basophil rather than the megakaryocytic differentiation potential of UT7D1 cells. I ndeed, in addition to HDC mRNA, they express spontaneously several other mR NA coding for molecules present in basophils (Fc epsilon RI, CCR3, IL-4R al pha, IL-5R alpha). Furthermore, the basophil antigen Bsp-1 is displayed on the surface of some UT7D1 cells in response to PMA concomitantly with incre ased histamine synthesis and mRNA expression of typical basophil-derived cy tokines (IL-6, IL-4, and IL-13). Nevertheless, PMA cannot sustain the diffe rentiation of this lineage, because mRNAs for basophil markers gradually di minish during long-term culture, whereas molecules associated with the mega karyocytic lineage remain prominent. In support of the notion that HDC acti vity is not related with megakaryopoiesis, we show that PMA-induced CD41 ex pression and PDGF transcription occurs in the K562 cells, though neither HD C mRNA nor any known basophil marker are expressed in these conditions. In contrast, all these markers are expressed in the basophilic leukemia cell l ine KU812F. Interestingly, the megakaryocytic cell line HEL produces also s ubstantial amounts of histamine and expresses Fc epsilon RI, thus revealing its basophil differentiation potential. HEL as well as KU812F need not be stimulated with PMA to react with Bsp-l mAb, suggesting that they are more engaged into the basophil differentiation scheme than UT7D1. Other leukemic cell lines unrelated to the megakaryocyte or basophil lineage, like HL60 a nd U937 do neither synthesize histamine nor express basophil markers before or after PMA stimulation. To our knowledge, this is the first evidence for a factor-dependent cell line with megakaryocyte/basophil bipotentiality wi th which early stages of basophil commitment can be analyzed. (C) 1999 Inte rnational Society for Experimental Hematology. Published by Elsevier Scienc e Inc.