title: Histamine as an autocrine regulator of leukemic cell proliferation.
abstract: We examined leukemic lymphocyte precursors from ALL patients as well as immortalized ALL cell lines for cytoplasmic histamine expression. The histamine levels ranged from 10.8 pg/10(6) cells to 82.2 pg/10(6) cells in ALL cell lines (N=4) and from 12.5 pg/10(6) cells to 1235.4 pg/10(6) cells for primary leukemic cells from ALL patients (N=13). The presence of histamine in the cytoplasm of these ALL cells was also confirmed by immunostaining using a polyclonal rabbit anti-histamine antibody. Notably, the histamine receptor blocker diphenhydramine inhibited the clonogenic growth of ALL cells by >90% prompting the hypothesis that histamine may be an autocrine regulator of ALL cell proliferation. Our study suggests that histamine receptor blockers may therefore be useful for the treatment of therapy-refractory ALL.
authors.affiliation: Department of Allergy and Inflammatory Diseases, Parker Hughes Cancer Center Hughes Institute, St. Paul, MN 55113, USA.
authors.forename: R
authors.initials: R
authors.lastname: Malaviya
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D000293:Adolescent; D019898:Autocrine Communication; D002455:Cell Division / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004155:Diphenhydramine / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006632:Histamine / Q000096:biosynthesis / Q000502:physiology*; D006633:Histamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D011968:Receptors, Histamine / Q000378:metabolism; D014410:Tumor Stem Cell Assay
chemical_list: D006633:Histamine Antagonists; D011968:Receptors, Histamine; D006632:Histamine; D004155:Diphenhydramine; D006640:Histidine Decarboxylase