Histamine as an autocrine regulator of leukemic cell proliferation

We examined leukemic lymphocyte precursors from ALL patients as well as imm ortalized ALL cell lines for cytoplasmic histamine expression. The histamin e 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 prim ary leukemic cells from ALL patients (N=13). The presence of histamine in t he cytoplasm of these ALL cells was also confirmed by immunostaining using a polyclonal rabbit anti-histamine antibody. Notably, the histamine recepto r blocker diphenhydramine inhibited the clonogenic growth of ALL cells by > 90% prompting the hypothesis that histamine may be an autocrine regulator o f ALL cell proliferation. Our study suggests that histamine receptor blocke rs may therefore be useful for the treatment of therapy-refractory ALL.