Remission maintenance in acute myeloid leukemia: impact of functional histamine H2 receptors expressed by leukemic cells

Haematologica. 2012 Dec;97(12):1904-8. doi: 10.3324/haematol.2012.066399. Epub 2012 Jun 11.


Post-consolidation immunotherapy with histamine dihydrochloride and interleukin-2 has been shown to improve leukemia-free survival in acute myeloid leukemia in a phase III trial. For this study, treatment efficacy was determined among 145 trial patients with morphological forms of acute myeloid leukemia as defined by the French-American-British classification. Leukemia-free survival was strongly improved in M4/M5 (myelomonocytic/monocytic) leukemia but not in M2 (myeloblastic) leukemia. We also analyzed histamine H(2) receptor expression by leukemic cells recovered from 26 newly diagnosed patients. H(2) receptors were typically absent from M2 cells but frequently expressed by M4/M5 cells. M4/M5 cells, but not M2 cells, produced reactive oxygen species that triggered apoptosis in adjacent natural killer cells. These events were significantly inhibited by histamine dihydrochloride. Our data demonstrate the presence of functional histamine H(2) receptors on human AML cells and suggest that expression of these receptors by leukemic cells may impact on the effectiveness of histamine-based immunotherapy.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Flow Cytometry
  • Follow-Up Studies
  • Histamine / pharmacology
  • Histamine Agonists / pharmacology
  • Humans
  • In Situ Hybridization, Fluorescence
  • Interleukin-2 / therapeutic use
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / metabolism
  • Killer Cells, Natural / pathology
  • Leukemia, Myeloid, Acute / classification
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / mortality
  • Leukemia, Myeloid, Acute / therapy*
  • Middle Aged
  • Prognosis
  • Reactive Oxygen Species / metabolism
  • Receptors, Histamine H2 / metabolism*
  • Remission Induction
  • Survival Rate


  • Histamine Agonists
  • Interleukin-2
  • Reactive Oxygen Species
  • Receptors, Histamine H2
  • Histamine