Histamine as an autocrine regulator of leukemic cell proliferation.
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.
Malaviya
R
R
Department of Allergy and Inflammatory Diseases, Parker Hughes Cancer Center Hughes Institute, St. Paul, MN 55113, USA.
Uckun
F M
FM
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
D006633:Histamine Antagonists; D011968:Receptors, Histamine; D006632:Histamine; D004155:Diphenhydramine; D006640:Histidine Decarboxylase