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/10⁶ cells to 82.2 pg/10⁶ cells in ALL cell lines (N = 4) and from 12.5 pg/10⁶ cells to 1235.4 pg/10⁶ 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.